Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

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

Optical modeling of aspherical lenses: a human eye study

We have been developing a computational code to project optical lenses, with low aberration effects. Our main interest is model the human eye, particularly, project special corrective lenses. As the lens shape is the focus of the optimization, we have coupled a ray tracing method with Monte Carlo techniques. The initial results indicated that the algorithm must be improved in terms of resolution and reliability.

Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers

Genotoxic effects linking cigarette smoking with lung cancer have not been consistently demonstrated, therefore claims for the cause-effect relationships are vigorously contested. Using matched populations of 22 lung cancer patients who have been cigarette smokers (LCP), 22 non-cancerous cigarette smokers (SC) and 13 non-smokers (NSC), we have applied the fluorescence in situ hybridization (FISH) tandem probe assay to elucidate the frequency of chromosome breakage among the participants. Two probes were used, a classical satellite probe which hybridizes to the large heterochromatin region of chromosome 1, and an alpha-satellite probe which targets a small region adjacent to the heterochromatin probe. The highest frequency of structural aberrations was observed in LCP (1.4 +/- 0.1) followed by SC (1.25 +/- 0.1) and NSC (0.4 +/- 0.1). Aberration frequencies were not significantly different between LCP and SC (p > 0.05), however, a statistically significant difference was detected between the smoker populations combined (LCP and SC) and the NSC (p < 0.001). The breakage frequencies showed a positive correlation with duration of smoking for LCP (r = 0.5; p < 0.01), but not for SC (P > 0.05). In addition, the aberration frequencies were influenced by the inheritance of polymorphic glutathione S-transferase (GST) genes. LCPs missing one or the other GST (GSTM1 or GSTT1) genes were found to have significantly higher chromosome breaks compared to LCPs with both genes present (p < 0.05), Our data indicate that genetic predisposition and chromosome aberrations may be mechanistically related to the initiation of lung carcinogenesis; therefore, they may be useful biomarkers for lung cancer among cigarette smokers. (C) 1997 Elsevier B.V. B.V.

Anticlastogenic effect of aqueous extracts of Agaricus blazei on CHO-k1 cells, studying different developmental phases of the mushroom

The Agaricus blazei Murill (ABM) mushroom, known as the sun mushroom, is native to Brazil and has become known for its medicinal properties. This study examined the anticlastogenic effect of Agaricus blazei in Chinese hamster ovary cells, CHO-k1, by means of a chromosome aberration test using methyl methanesulphonate (MMS, 10(-4)M) as the DNA damage inducing agent. Two mushroom lines were used, ABM 99/26 and ABM 97/11, and the latter was used in the young (Y) and sporulating (S) developmental phases. The cells were treated for 12 h with MMS alone or combined with aqueous extracts of A. blazei at a final concentration of 0.15%, which were prepared at three different temperatures: (a) hot (60 degreesC), (b) room temperature (25 degreesC) and (c) chilled (4 degreesC). Mushroom extracts showed a marked anticlastogenic effect against DNA damage, as evidenced by a decrease in the number of cells with breaks, regardless of the line used, or the developmental stage or the temperature at which the extract was prepared. Generally, the extracts were more effective in reducing the isochromatid type breaks. The data obtained suggest that extracts of A. blazei mushroom are anticlastogenic under the conditions tested, mainly during the G1 and S stages of the cell cycle, where chromosome breaks of the isochromatid type are produced by the MMS agent. (C) 2003 Elsevier Ltd. All rights reserved.

Mutagenic and cytotoxic activity of an isocoumarin (Paepalantine) isolated from Paepalanthus vellozioides

A new isocoumarin with antimicrobial activity was isolated from Paepalanthus vellozioides (a native Brazilian plant) and called paepalantine. This study was carried out to assess the mutagenic activity of this new agent in assays with Salmonella typhimurium TA100, TA98, and TA102 and in Chinese hamster ovary (CHO) cell cultures, as well as cytotoxicity to McCoy cells. Paepalantine caused a significant dose-dependent increase in the frequency of revertants in the three strains used in the assay, both with and without S9 mix, in concentrations varying from 2 to 128 mu g/ plate. The mutagenicity was confirmed in assays with CHO cells treated in the G(1), S, and G(2) phases of the cell cycle. There was an increase in the chromosomal aberration frequency, mainly in the G(2) phase. Furthermore, the mitotic index of the treated cultures (40,80, and 160 mu g/ml) was significantly lower, indicating cytotoxicity. The midpoint cytotoxicity values to McCoy cells by the neutral red (NR) and microculture tetrazolium (MTT) techniques resulted in a NR50, and MTT50 of 30 and 38 mu g/ml, respectively. Alterations to the paepalantine structure are suggested to reduce its mutagenic and cytotoxic activity in investigations for its antineoplasic potential (C) 1997 Wiley-Liss, Inc.

Chromosome aberrations as a predictor of clinical outcome for smoking associated lung cancer

The ability to identify individuals at greatest risk of developing lung cancer can significantly enhance the efficacy of intervention modalities. One strategy for identifying these individuals is through biomarkers that reflect the severity of their cancer. In the present study, we evaluated 22 lung cancer patients and 35 controls to determine whether the frequency of chromosome aberrations was significantly associated with specific clinical variables such as the histological type, grade and stage of the turners. Chromosome aberrations (expressed as total breaks) were investigated on chromosome 1 in interphase nuclei obtained from blood Lymphocytes of the study participants using the fluorescence in situ hybridization (FISH) chromosome aberration assay. Our results indicate a significant linear increase (P = 0.01) in the level of breaks with respect to the grade of the carcinoma. The poorly differentiated tumors had a significantly higher level of chromosome breaks mean +/- SD (1.7 +/- 0.46) as compared to the well differentiated tumors (0.98 +/- 0,23, P < 0,05). These results indicate that chromosome aberrations, as determined by the FISH assay, can be used as a biomarker for identifying individuals with aggressive types of lung cancer and potentially, as a predictor for prognostic outcome of the disease. (C) 2000 Elsevier B.V. Ireland Ltd. All rights reserved.

Genotoxicity and mutagenicity of water samples from the Monjolinho River (Brazil) after receiving untreated effluents

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

Multiple cytogenetic clones in a basal cell carcinoma

Chromosome analysis of short-term culture of a basal cell carcinoma showed five clonal chromosome abnormalities, t(9;14)(q12 or q13;p11), del(1)(q23 or q25), trisomy 5, trisomy 7, and monosomy X. In addition, several nonclonal structural and numerical changes were seen in the tumor cells.

Distribution of a Robertsonian translocation in goats

Two hundred and five animals were cytogenetically studied. They were related to a male goat called 'Harald', imported from Switzerland, who was a t 5 15 chromosomic translocation carrier. 29.27% of the analyzed animals were heterozygous and 4.88% were homozygous. All carrying animals were found in Botucatu, Limeira and São Manuel city in Brazil. Descendants of this buck were sold in several regions of Brazil, and may have spread this aberration. © 1992.

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients

Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2 when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.

Human chromosome aberrations induced in vitro by Paracoccidioides brasiliensis glycoproteic component (GP 43)

The in vitro cytogenetic effects of the 43-kDa molecular mass exocellular glycoproteic component (GP 43) from Paracoccidioides brasiliensis were studied in cultures from human lymphocytes. The sample included 10 healthy, white, non-smoking, non-related males (mean age of 31.3 ± 8.2 years). Besides the control, three concentrations of GP 43 (0.125, 1.25 and 5 μg/ml) were used. In each group, around 1000 cells were examined in search of chromosome aberrations, and 30,000 metaphases were analysed for the determination of the Mitotic Index. The authors conclude that GP 43 most probably causes inhibition of the cell cycle and aneugenic and clastogenic effects.

Cytogenetic evaluation of 20 primary breast carcinomas

Chromosome analysis was performed on samples from 20 Brazilian patients with breast cancer. All the samples were from untreated patients who presented the clinical symptoms for months or years before surgical intervention. Six cases showed axillary lymph node metastases. Clonal chromosome abnormalities were detected in all cases. The numerical alterations most frequently observed involved the loss of chromosomes X, 19, 20, and 22 followed by gain of chromosomes 9 and 8. Among the structural anomalies observed, there was preferential involvement of chromosomes 11, 6, 1, 7, 3, and 12, supporting previous reports that these chromosomes may harbour genes of importance in the development of breast tumors. Two cases with a family history of breast cancer had in common total or partial trisomy 1.

Clonal chromosome abnormalities found in three non-neoplastic proliferative brain lesions

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

Chromosome damage induced by 5-azacytidine under the influence of caffeine or cytosine arabinoside in CHO-K1 (wild-type) and XRS-5 (mutant) cell lines

5-azacytidine (5-azaC) treatment combined with cytosine arabinoside (ara-C) or caffeine were performed in vitro in Chinese hamster cells, CHO-K1 (wild-type) and xrs-5 (mutant) cell lines, in order to compare the cell response to the induction of chromosomal aberrations. Exponentially growing cells were treated with 5-azaC (4-16 uM) for 1 h, the cells were washed and incubated for 7 h, and 500 uM caffeine or 5 uM ara-C were added to the cultures for the last 2 h. In both cell lines, 5-azaC induced a significantly increase (P<0.01) in the frequencies of aberrations; in the combined treatments (5-azaC + Ara-C), a significant reduction (P<0.05) was observed for the aberrations which were randomly distributed. Caffeine had no influence at the same conditions. 5-azaC induced-DNA lesions were probably processed at S/G2 phase in a common pathway in both cell lines, but alternatively, 5-azaC may cause xrs-5 cells to revert to the wild-type.