Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney

Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.

Re-evaluation of the effect of smoking on the methylation of N-terminal valine in haemoglobin

In view of the established extrapulmonary cancer sites targeted by smoking a multiplicity of compounds, and mechanisms might be involved. It has been debated that smoking caused increased incidence of N-methylvaline at the N-terminus of haemoglobin. Because this could indicate a relevance of methylating nitrosamines in tobacco smoke, data are presented from an industrial cohort of 35 smokers and 21 non-smokers repeatedly monitored between 1994 and 1999. In general, N-methylvaline adduct levels in haemoglobin of smokers were approximately 50% higher than those of non-smokers. The smoking-induced methylation of haemoglobin is likely to be caused by dimethylnitrosamine (N-nitroso-dimethylamine), a major nitrosamine in side-stream tobacco smoke. The biomonitoring data emphasise the potential value of N-methylvaline as a smoking-related biomarker and call for intensified research on tobacco smoke compounds that lead to macromolecular methylation process.

Sexual selection in a tropical fruit fly : role of a plant derived chemical in mate choice

The specific mechanisms by which selective pressures affect individuals are often difficult to resolve. In tephritid fruit flies, males respond strongly and positively to certain plant derived chemicals. Sexual selection by female choice has been hypothesized as the mechanism driving this behaviour in certain species, as females preferentially mate with males that have fed on these chemicals. This hypothesis is, to date, based on studies of only very few species and its generality is largely untested. We tested the hypothesis on different spatial scales (small cage and seminatural field-cage) using the monophagous fruit fly, Bactrocera cacuminata. This species is known to respond to methyl eugenol (ME), a chemical found in many plant species and one upon which previous studies have focused. Contrary to expectation, no obvious female choice was apparent in selecting ME-fed males over unfed males as measured by the number of matings achieved over time, copulation duration, or time of copulation initiation. However, the number of matings achieved by ME-fed males was significantly greater than unfed males 16 and 32 days after exposure to ME in small cages (but not in a field-cage). This delayed advantage suggests that ME may not influence the pheromone system of B. cacuminata but may have other consequences, acting on some other fitness consequence (e.g., enhancement of physiology or survival) of male exposure to these chemicals. We discuss the ecological and evolutionary implications of our findings to explore alternate hypotheses to explain the patterns of response of dacine fruit flies to specific plant-derived chemicals.

Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues : factors influencing renal carcinogenesis induced by xenobiotics

In general, the biological activation of nephrocarcinogenic chlorinated hydrocarbons proceeds via conjugatiton with glutathione. It has mostly been assamed that the main site of initial conjugation is the liver, followed by a mandatory transfer of intermediates to the kidney. It was therefore of interest to study the enzyme activities of subgroups of glutathione transferases (GSTs) in renal cancers and the surrounding normal renal tissues of the same individuals (n = 21). For genotyping the individuals with respect to known polymorphic GST isozymes the following substrates with differential specificity were used: 1-chloro-2,4-dinitrobenzene for overall GST activity (except GST θ); 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole for GST α; 1,2-dichloro-4-nitro-benzene for GST μ; ethacrynic acid and 4-vinylpyridine for GST π; and methyl chloride for GST θ. In general, the normal tissues were able to metabolize the test substrates. A general decrease in individual GST enzyme activities was apparent in the course of cancerization, and in some (exceptional) cases individual activities, expressed in the normal renal tissue, were lost in the tumour tissue. The GST enzyme activities in tumours were independent of tumour stage, or the age and gender of the patients. There was little influence of known polymorphisms of GSTM1, GSTM3 and GSTP1 upon the activities towards the test substrates, whereas the influence of GSTT1 polymorphism on the activity towads methyl chloride was straightforward. In general, the present findings support the concept that the initial GST-dependent bioactivation step of nephrocarcinogenic chlorinated hydrocarbons may take place in the kidney itself. This should be a consideration in toxicokinetic modelling.

Female Entrepreneurship in Australia: Revisited

This paper is a ten-year follow-up on a study conducted in 1995 that profiled women entrepreneurs in Australia (Bennett and Dann 2000). The aim of the paper is to identify changes in demographic profile, motivation and personality traits of women entrepreneurs over the past ten years by replicating a study from1995 and reporting the results.

Geek goddesses go to school : A study of female pre-service teachers in information technology courses

Various reasons have been proffered for female under-representation in tertiary information technology (IT) courses and the IT industry with most relating to cultural moirés. The 2006 Geek Goddess calendar was designed to alter IT’s “geeky image” and the term is used here to represent young women enrolled in pre-service IT teaching courses. Their special mix of IT and teaching draws on conflicting stereotypes and represents a micro-climate which is typically lost in studies of IT occupations because of the aggregation of all IT roles. This paper will report on a small-scale investigation of female students (N=25) at a university in Queensland (Australia) studying to become teachers of secondary IT subjects. They are entering the IT industry, gendered as a “male” occupation, through the safe space of teaching a discipline allied to feminine qualities of nurturing. They are “geek goddesses” who – perhaps to balance the masculine and feminine of these occupations - have decided to go to school rather than into corporations or government.