Pollen mother cells of Tradescantia clone 4430 and Tradescantia pallida var. purpurea are equally sensitive to the clastogenic effects of X-rays

The Tradescantia micronucleus test is a sensitive bioassay for mutagenesis that may be employed both under field and laboratory conditions. This test has been standardized mostly on the basis of the results obtained with clone 4430. However, this clone is not well adapted to tropical weather, frequently showing problems with growth and flowering. In addition, it is attacked by parasites and insects, a fact that limits its use in field studies aiming at the biomonitoring of air pollution. In the city of São Paulo, Tradescantia pallida (Rose) Hunt. var. purpurea Boom is widely distributed as an ornamental plant in gardens and along roadsides and streets, mostly because of its natural resistance and its easy propagation. In this report, we present dose-response curves indicating that the sensitivity of T. pallida and clone 4430 to X-radiation (1, 10, 25 and 50 cGy) is similar. The results confirm our previous suggestion that T. pallida represents a good alternative for in situ mutagenesis testing in tropical regions, especially biomonitoring studies in which the exposure conditions may not be fully controllable.

Caractérisation de la composante toxicocinétique du facteur d’ajustement pour la variabilité interindividuelle utilisé en analyse du risque toxicologique

Un facteur d’incertitude de 10 est utilisé par défaut lors de l’élaboration des valeurs toxicologiques de référence en santé environnementale, afin de tenir compte de la variabilité interindividuelle dans la population. La composante toxicocinétique de cette variabilité correspond à racine de 10, soit 3,16. Sa validité a auparavant été étudiée sur la base de données pharmaceutiques colligées auprès de diverses populations (adultes, enfants, aînés). Ainsi, il est possible de comparer la valeur de 3,16 au Facteur d’ajustement pour la cinétique humaine (FACH), qui constitue le rapport entre un centile élevé (ex. : 95e) de la distribution de la dose interne dans des sous-groupes présumés sensibles et sa médiane chez l’adulte, ou encore à l’intérieur d’une population générale. Toutefois, les données expérimentales humaines sur les polluants environnementaux sont rares. De plus, ces substances ont généralement des propriétés sensiblement différentes de celles des médicaments. Il est donc difficile de valider, pour les polluants, les estimations faites à partir des données sur les médicaments. Pour résoudre ce problème, la modélisation toxicocinétique à base physiologique (TCBP) a été utilisée pour simuler la variabilité interindividuelle des doses internes lors de l’exposition aux polluants. Cependant, les études réalisées à ce jour n’ont que peu permis d’évaluer l’impact des conditions d’exposition (c.-à-d. voie, durée, intensité), des propriétés physico/biochimiques des polluants, et des caractéristiques de la population exposée sur la valeur du FACH et donc la validité de la valeur par défaut de 3,16. Les travaux de la présente thèse visent à combler ces lacunes. À l’aide de simulations de Monte-Carlo, un modèle TCBP a d’abord été utilisé pour simuler la variabilité interindividuelle des doses internes (c.-à-d. chez les adultes, ainés, enfants, femmes enceintes) de contaminants de l’eau lors d’une exposition par voie orale, respiratoire, ou cutanée. Dans un deuxième temps, un tel modèle a été utilisé pour simuler cette variabilité lors de l’inhalation de contaminants à intensité et durée variables. Ensuite, un algorithme toxicocinétique à l’équilibre probabiliste a été utilisé pour estimer la variabilité interindividuelle des doses internes lors d’expositions chroniques à des contaminants hypothétiques aux propriétés physico/biochimiques variables. Ainsi, les propriétés de volatilité, de fraction métabolisée, de voie métabolique empruntée ainsi que de biodisponibilité orale ont fait l’objet d’analyses spécifiques. Finalement, l’impact du référent considéré et des caractéristiques démographiques sur la valeur du FACH lors de l’inhalation chronique a été évalué, en ayant recours également à un algorithme toxicocinétique à l’équilibre. Les distributions de doses internes générées dans les divers scénarios élaborés ont permis de calculer dans chaque cas le FACH selon l’approche décrite plus haut. Cette étude a mis en lumière les divers déterminants de la sensibilité toxicocinétique selon le sous-groupe et la mesure de dose interne considérée. Elle a permis de caractériser les déterminants du FACH et donc les cas où ce dernier dépasse la valeur par défaut de 3,16 (jusqu’à 28,3), observés presqu’uniquement chez les nouveau-nés et en fonction de la substance mère. Cette thèse contribue à améliorer les connaissances dans le domaine de l’analyse du risque toxicologique en caractérisant le FACH selon diverses considérations.

Perfil de exposición ocupacional a polvo de cemento y sílice cristalina en procesos de cementación y Fracturamiento hidráulico en el sector Oil & Gas en Colombia: un estudio retrospectivo (2009 – 2013).

La exposición a polvo de cemento y sílice ha sido estudiada por años en países como Estados Unidos y Canadá, cuando el polvo de cemento se inhala durante diferentes actividades, se puede ocasionar afectación del tracto respiratorio de las personas expuestas. El estudio “Perfil de exposición ocupacional a polvo de cemento y sílice cristalina en procesos de cementación y Fracturamiento hidráulico en el sector Oil & Gas en Colombia: un estudio retrospectivo (2009 – 2013).” Permitió identificar las actividades funcionales que representan un riesgo potencial por la presencia de partículas aerosuspendidas, analizar una base de datos que reúne cerca de 18298 registros de evaluaciones higiénicas en el sector Oil & Gas, realizar posteriormente el cálculo de material particulado en la fracción respirable y sílice cristalina aplicables para cada proceso y el procesamiento de los datos estadísticamente, confrontar estos estimadores estadísticos con los valores límites permisibles definidos por el gobierno nacional, los resultados incluyeron la caracterización de un perfil de exposición ocupacional por actividad funcional para el proceso de cementación, la identificación de los trabajadores más expuestos según las condiciones de exposición y cuáles de estos perfiles superan los límites máximos permisibles para un turno de trabajo de 12 horas, esta información permitirá a los profesionales de la salud e higiene laboral orientar actividades de seguimiento, vigilancia y control en los grupos de exposición similar específicos. Para el proceso de fracturamiento hidráulico los datos encontrados no fueron estadísticamente significativos.

Profile of cortisol, glycaemia, and blood parameters of American Bullfrog tadpoles Lithobates catesbeianus exposed to density and hypoxia stressors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do período e volume de aplicação na segurança dos tratoristas aplicando herbicidas na cultura de cana-de-açúcar (Saccharum spp.)

O objetivo deste trabalho foi avaliar os efeitos do período e volume de aplicação na segurança da atividade de tratoristas aplicando herbicidas na cultura de cana-de-açúcar com o pulverizador de barra montado em trator e a eficiência de equipamentos de proteção individual (EPIs) e de uma cabina acoplada ao trator. As exposições dérmicas de 13 condições de trabalho foram avaliadas e analisadas estatisticamente por meio do delineamento inteiramente ao acaso e do esquema fatorial 3 x 2 x 2 + 1. O fator A foi a condição de exposição: 1) exposição dérmica potencial (EDP) - sem nenhuma medida de segurança; 2) exposição com cabina no trator (Cabina); e 3) exposição com as vestimentas (EPI). O fator B foi o volume de aplicação: 1) 200 L ha-1 e 2) 100 L ha-1; e o fator C foi o período de aplicação: 1) diurno e 2) noturno. Como testemunha foi avaliada a EDP do tratorista aplicando na atividade usual de 300 L de calda ha-1, no período diurno. As exposições dérmicas (EDs) aos herbicidas considerados nessas condições de trabalho foram estimadas por meio de dados substitutos das EDs avaliadas ao cátion Cu+2 adicionado como traçador nas caldas aplicadas. O pulverizador utilizado foi do modelo PJ 600, com barra de 12 m de comprimento e 24 bicos de jato plano TT 110 04 ou TT 110 02. As 13 condições de trabalho avaliadas foram classificadas como seguras (MS>1) para o tratorista aplicando os herbicidas glyphosate (48% i.a.), MSMA (48%), diuron (46,8%) + hexazinone (13,2%), clomazone (50%), sulfentrazone (50%), ametryne (50%), diuron (50%), isoxaflutole (75%), metribuzin (48%), 2,4-D (80,6%), ametryne (30%) + clomazone (20%), ametryne (73,25%) + trifloxysulfuron (1,85%) e tebuthiuron (80 %) e inseguras para o herbicida atrazine (50%), nos dois períodos e nos três volumes de aplicação, e ametryne (50%), na aplicação diurna e 100 L de calda ha-1. As aplicações noturnas e os volumes de aplicação reduzidos tornaram as condições de trabalho mais seguras, exceto para o atrazine. A eficiência dos EPIs para a aplicação de 300 L ha-1 variou de 69,5 a 89,3%, e a da cabina do trator variou entre 76,4 e 83,3%, em relação aos volumes reduzidos de 100 e 200 L ha-1.

Can Eucalyptus invade native forest fragments close to commercial stands?

Some Eucalyptus species are widely used as a plantation crop in tropical and subtropical regions. One reason for this is the diversity of end uses, but the main reason is the high level of wood production obtained from commercial plantings. With the advancement of biotechnology it will be possible to expand the geographical area in which eucalypts can be used as commercial plantation crops, especially in regions with current climatic restrictions. Despite the popularity of eucalypts and their increasing range, questions still exist, in both traditional planting areas and in the new regions: Can eucalypts invade areas of native vegetation, causing damage to natural ecosystems biodiversity?The objective of this study it was to assess whether eucalypts can invade native vegetation fragments in proximity to commercial stands, and what factors promote this invasive growth. Thus, three experiments were established in forest fragments located in three different regions of Brazil. Each experiment was composed of 40 plots (1 m(2) each one), 20 plots located at the border between the forest fragment and eucalypts plantation, and 20 plots in the interior of the forest fragments. In each experimental site, the plots were paired by two soil exposure conditions, 10 plots in natural conditions and 10 plots with soil exposure (no plant and no litter). During the rainy season, 2 g of eucalypts seeds were sown in each plot, including Eucalyptus grandis or a hybrid of E. urophylla x E. grandis, the most common commercial eucalypt species planted in the three region. At 15, 30, 45, 90, 180, 270 and 360 days after sowing, we assessed the number of seedlings of eucalypts and the number of seedlings of native species resulting from natural regeneration. Fifteen days after sowing, the greatest number of eucalypts seedlings (37 m(-2)) was observed in the plots with lower luminosity and exposed soil. Also, for native species, it was observed that exposed soil improved natural germination reaching the highest number of 163 seedlings per square meter. Site and soil exposure were the factors that have the greatest influence on seed germination of both eucalypt and native species. However, 270 days after sowing, eucalypt seedlings were not observed at any of the three experimental sites. The result shows the inability of eucalypts to adapt to condition outside of their natural range. However, native species demonstrated their strong capacity for natural regeneration in forest fragments under the same conditions where eucalypts were seeded. (C) 2011 Elsevier B.V. All rights reserved.

Migration of Tinuvin P, a UV stabilizer, from PET bottles into fatty-food simulants

Tinuvin P migration from Polyethyleneterephthalate (PET) bottles was investigated using several fatty-food simulants such as olive oil, soybean oil, n-heptane and iso-octane, at exposure conditions of 2-10 days at 40 degrees C (total immersion). The stability of several UV stabilizers (BHT, Cyasorb UV 5411, Tinuvin P, Tinuvin 326 and Tinuvin 327) in n-heptane and iso-octane was also studied. After 10 days at 40 degrees C, losses of 6% and 20% in iso-octane and n-heptane respectively, were verified for Tinuvin P. Other UV stabilizers at the same experimental conditions showed higher losses (up to 30% for Tinuvin 327). These results confirm that, when carrying out specific migration studies, the stability of the substance of interest should be established in the food simulant to avoid underestimating the real migration behaviour. In order to quantify UV stabilizer migration, n-heptane and iso-octane solutions were concentrated and directly analysed by SIM mode GC-MS. For olive and soybean oils, Tinuvin P was isolated using size-exclusion chromatography and quantified by SIM mode GC-MS. Iso-octane proved to be a move suitable fatty-food simulant than n-heptane for the migration study of Tinuvin P from PET. Higher levels of Tinuvin P migrated to olive and soybean oils rather than to n-heptane. These results suggest that the MERCOSUL recommended official methods for specific migration studies should be revised since the migration levels using n-heptane as a fatty-food simulant could be underestimated when compared to edible oils. Copyright (C) 1999 John Wiley & Sons, Ltd.

The influence of oxygen in the photoexpansion of GaGeS glasses

Irreversible photoexpansion and photobleaching effect has been observed in amorphous Ga10Ge25S65 glass when its surface was exposed to light with energy greater than the band gap, 3.52 eV. The magnitude of the expansion of GaGeS glasses depends on the exposure conditions. Extended X-ray absorption fine structure (EXAFS) spectroscopy and Rutherford backscattering spectrometry (RBS) have been used to identify the chemical nature of the glass samples before and after illumination. The quantitative analysis of the EXAFS data leads to a two-shell model of 0.5 oxygen atoms at 2.01 Angstrom and 3.6 sulfur atoms at a 2.20 Angstrom. RBS technique demonstrated that chemical composition of the glass surface after irradiation is oxygen rich. The existence of Ge-O bonds in the glass after illumination was also confirmed by infrared measurements. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Comparison of direct digital and conventional imaging with Ekta Speed Plus and INSIGHT films for the detection of approximal caries

Purpose: To evaluate the accuracy of approximal caries detection comparing enhanced and unenhanced Sidexis CCD-based digital image with Ektaspeed Plus and INSIGHT films. Methods: Fifty-two extracted premolars were imaged under identical standardized geometric and exposure conditions. Four observers, using five points confidence scale, rated 104 approximal surfaces for the presence or absence of carious lesions by means of four image modalities: (1) observer enhanced; (2) unenhanced Sidexis displays; (3) E speed films and (4) F speed film. Histologic sections served as validating criterion for the presence and depth of carious lesions. Diagnostic accuracy was measured as the area beneath the ROC curve. Results: Mean ROC (receiver operating characteristic) curve areas for approximal surfaces were 0.865 (E speed), 0.856 (F speed), 0.816 (unenhanced Sidexis) and 0.776 (observer enhanced). There were no significant differences between unenhanced digital Sidexis and films. Observer enhanced Sidexis images exhibited a statistically significant lower diagnostic accuracy than the film images for two of the observers.

Influence of fluoride-releasing restorative material on root dentine secondary caries in situ

The usefulness of fluoride-releasing restorations in secondary caries prevention may be questioned because of the presence of other common sources of fluoride and because of ageing of the restorations. This study tested the hypothesis that glass-ionomer cement restorations, either aged or unaged, do not prevent secondary root caries, when fluoride dentifrice is frequently used. Sixteen volunteers wore palatal appliances in two phases of 14 days, according to a 2 x 2 crossover design. In each phase the appliance was loaded with bovine root dentine slabs restored with either glass-ionomer or resin composite, either aged or unaged. Specimens were exposed to cariogenic challenge 4 times/day and to fluoridated dentifrice 3 times/day. The fluoride content in the biofilm (FB) formed on slabs and the mineral loss (Delta Z) around the restorations were analysed. No differences were found between restorative materials regarding the FB and the Delta Z, for either aged (p = 0.792 and p = 0.645, respectively) or unaged (p = 1.00 and p = 0.278, respectively) groups. Under the cariogenic and fluoride dentifrice exposure conditions of this study, the glass-ionomer restoration, either aged or unaged, did not provide additional protection against secondary root caries. Copyright (c) 2006 S. Karger AG, Basel.

Tailoring the refractive index of Ge-S based glass for 3D embedded waveguides operating in the mid-IR region

The photosensitivity of GeSx binary glasses in response to irradiation to femtosecond pulses at 800 nm is investigated. Samples with three different molecular compositions were irradiated under different exposure conditions. The material response to laser exposure was characterized by both refractometry and micro-Raman spectroscopy. It is shown that the relative content of sulfur in the glass matrix influences the photo-induced refractive index modification. At low sulfur content, both positive and negative index changes can be obtained while at high sulfur content, only a positive index change can be reached. These changes were correlated with variations in the Raman response of exposed glass which were interpreted in terms of structural modifications of the glass network. Under optimized exposure conditions, waveguides with positive index changes of up to 7.8x10−3 and a controllable diameter from 14 to 25 μm can be obtained. Direct inscription of low insertion losses (IL = 3.1 – 3.9 dB) waveguides is demonstrated in a sample characterized by a S/Ge ratio of 4. The current results open a pathway towards the use of Ge-S binary glasses for the fabrication of integrated mid-infrared photonic components.

Biofilms on exposed monumental stones: mechanism of formation and development of new control methods

Within the stone monumental artefacts artistic fountains are extremely favorable to formation of biofilms, giving rise to biodegradation processes related with physical-chemical and visual aspect alterations, because of their particular exposure conditions. Microbial diversity of five fountains (two from Spain and three from Italy) was investigated. It was observed an ample similarity between the biodiversity of monumental stones reported in literature and that one found in studied fountains. Mechanical procedures and toxic chemical products are usually employed to remove such phototrophic patinas. Alternative methods based on natural antifouling substances are recently experimented in the marine sector, due to their very low environmental impact and for the bio settlement prevention on partially immersed structures of ships. In the present work groups of antibiofouling agents (ABAs) were selected from literature for their ability to interfere, at molecular level, with the microbial communication system “quorum sensing”, inhibiting the initial phase of biofilm formation. The efficacy of some natural antibiofoulants agents (ABAs) with terrestrial (Capsaicine - CS, Cinnamaldehyde - CI) and marine origin (Zosteric Acid - ZA, poly-Alkyl Pyridinium Salts – pAPS and Ceramium botryocarpum extract - CBE), incorporated into two commercial coatings (Silres BS OH 100 - S and Wacker Silres BS 290 - W) commonly used in stone conservation procedures were evaluated. The formation of phototrophic biofilms in laboratory conditions (on Carrara marble specimens and Sierra Elvira stone) and on two monumental fountains (Tacca’s Fountain 2 - Florence, Italy and Fountain from Patio de la Lindaraja - Alhambra Palace, Granada, Spain) has been investigated in the presence or absence of these natural antifouling agents. The natural antibiofouling agents, at tested concentrations, demonstrated a certain inhibitory effect. The silane-siloxane based silicone coating (W) mixing with ABAs was more suitable with respect to ethyl silicate coating (S) and proved efficacy against biofilm formation only when incompletely cured. The laboratory results indicated a positive action in inhibiting the patina formation, especially for poly-alkyl pyridinium salts, zosteric acid and cinnamaldehyde, while on site tests revealed a good effect for zosteric acid.

Corrosione atmosferica in area urbana-costiera di un acciaio Cor-Ten: studio del rilascio in ambiente dei metalli di lega

Cor-Ten is a particular kind of steel, belonging to low-alloyed steel; thanks to his aesthetic features and resistance to atmospheric corrosion, this material is largely used in architectural, artistic and infrastructural applications. After environmental exposure, Cor-Ten steel exhibits the characteristic ability to self-protect from corrosion, by the development of a stable and adherent protective layer. However, some environmental factors can influence the formation and stability of the patina. In particular, exposure of Cor-Ten to polluted atmosphere (NOx, SOx, O3) or coastal areas (marine spray) may cause problems to the protective layer and, as a consequence, a release of alloying metals, which can accumulate near the structures. Some of these metals, such as Cr and Ni, could be very dangerous for soils and water because of their large toxicity. The aim of this work was to study the corrosion behavior of Cor-Ten exposed to an urban-coastal site (Rimini, Italy). Three different kinds of commercial surface finish (bare and pre-patinated, with or without a beeswax covering) were examined, both in sheltered and unsheltered exposure conditions. Wet deposition brushing the specimens surface (leaching solutions) are monthly collected and analyzed to evaluate the extent of metal release and the form in which they leave the surface, for example, as water-soluble compounds or non-adherent corrosion products. Five alloying metals (Fe, Cu, Cr, Mn and Ni) and nine ions (Cl-, NO3-, NO2-, SO42-, Na+, Ca2+, K+, Mg2+, NH4+) are determined through Atomic Absorption Spectroscopy and Ion Chromatography, respectively. Furthermore, the evolution and the behaviour of the patina are periodically followed by surface investigations (SEM-EDS and Raman Spectroscopy). After two years of exposure, the results show that Bare Cor-Ten, cheaper than the other analyzed specimens, even though undergoes the greater mass variation, his metal release is comparable to the release of the pre-patinated samples. The behavior of pre-patinated steel, with or without beeswax covering, do not show particular difference. This exposure environment doesn’t allow a completely stabilization of the patina; nevertheless an estimate of metal release after 10 years of exposure points out that the environmental impact of Cor-Ten is very low: for example, the release of chromium in the soluble fraction is less than 10 mg if we consider an exposed wall of 10 m2.

Assessment of in vivo genotoxicity of the rodent carcinogen furan: evaluation of DNA damage and induction of micronuclei in mouse splenocytes

In recent years, several surveys have highlighted the presence of the rodent carcinogen furan in a variety of food items. Even though the evidence of carcinogenicity of furan is unequivocal, the underlying mechanism has not been fully elucidated. In particular, the role of genotoxicity in furan carcinogenicity is still not clear, even though this information is considered pivotal for the assessment of the risk posed by the presence of low doses of furan in food. In this work, the genotoxic potential of furan in vivo has been investigated in mice, under exposure conditions similar to those associated with cancer onset in the National Toxicology Program long-term bioassay. To this aim, male B6C3F1 mice were treated by gavage for 4 weeks with 2, 4, 8 and 15 mg furan/kg b.w./day. Spleen was selected as the target organ for genotoxicity assessment, in view of the capability of quiescent splenocytes to accumulate DNA damage induced by repeat dose exposure. The induction of primary DNA damage in splenocytes was evaluated by alkaline single-cell gel electrophoresis (comet assay) and by the immunofluorescence detection of foci of phosphorylated histone H2AX (gamma-H2AX). The presence of cross-links was probed in a modified comet assay, in which cells were irradiated in vitro with gamma-rays before electrophoresis. Chromosome damage was quantitated through the detection of micronuclei in mitogen-stimulated splenocytes using the cytokinesis-block method. Micronucleus induction was also assessed with a modified protocol, using the repair inhibitor 1-beta-arabinofuranosyl-cytosine to convert single-strand breaks in micronuclei. The results obtained show a significant (P < 0.01) increase of gamma-H2AX foci in mitogen-stimulated splenocytes of mice treated with 8 and 15 mg furan/kg b.w. and a statistically significant (P < 0.001) increases of micronuclei in binucleated splenocytes cultured in vitro. Conversely, no effect of in vivo exposure to furan was observed when freshly isolated quiescent splenocytes were analysed by immunofluorescence and in comet assays, both with standard and radiation-modified protocols. These results indicate that the in vivo exposure to furan gives rise to pre-mutagenic DNA damage in resting splenocytes, which remains undetectable until it is converted in frank lesions during the S-phase upon mitogen stimulation. The resulting DNA strand breaks are visualized by the increase in gamma-H2AX foci and may originate micronuclei at the subsequent mitosis.

AN INVESTIGATION OF THE MODIFYING EFFECTS OF VITAMIN A AND HYPOXIC CELL SENSITIZERS IN RADIATION CARCINOGENESIS IN MICE

The effect of vitamin A (retinyl acetate) and three hypoxic cell sensitizers (metronidazole, misonidazole and desmethylmisonidazole) on lung tumor development in strain A mice exposed to radiation was assessed.^ In experiments involving vitamin A, two groups of mice were fed a low vitamin A diet (< 100 IU/100g diet) while the two other groups were fed a high vitamin A diet (800 IU/100g diet). After two weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. The circulating level of plasma vitamin A in all four groups of mice was monitored. A difference in circulating vitamin A in the mice maintained on high and low vitamin A diet became evident by 20 weeks and continued for the duration of the experiment. Mice were killed 18, 26, and 40 weeks post irradiation, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post irradiation as compared to the irradiated group maintained on a low vitamin A diet (p < 0.05). Under the conditions of this experiment the development of pulmonary adenomas in irradiated strain A mice appears to relate directly to circulating levels of vitamin A.^ In the other experiment two dose levels of the hypoxic cell sensitizers, 0.2mg/g and 0.6mg/g, were used either alone or in combination with 900 rad of gamma radiation in a fractionated dose schedule of twice a week for three weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p < 0.10) in the higher dose group (0.6mg/g) of misonidazole but was not significantly different from the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with the control group. Thus, under the experimental exposure conditions used in this investigation, which were very similar to the exposure conditions occurring in clinical treatment, all three hypoxic cell sensitizers did not sensitize the mouse to the carcinogenic effects of gamma radiation.^