Physiological and nutritional factors modulating the gene expression in the liver of mice exposed transpacentary to arsenate.

There are suggestions that inorganic arsenic, a major drinking water contaminants in several countries, could act as a transplacental carcinogen in mice (Walkees et al.2004). There are also evidences that toxic responses following exposure to arsenic are strongly influenced by nutritional, phisiological and genetic factors (Vahter, 2000). In the frame of a project on the assessment of risk modifying factors modulating the health effects of environmental chemicals we are using an “arsenic in mice” experimental model to develop toxicogenomic approaches. In the present study, we used cDNA Macroarrays to investigate the effects of low protein intake, on the expression of 1185 cancer-related genes in the liver of male and female mice transplacentary exposed to arsenate by arsenate in drinking water during gestation. Female adult mice were fed either with standard rodent chow (18% protein rich) or with a protein deprived one (8%) forten days. Both groups of animals were also exposed to different concentrations of sodium arsenate in drinking water (0.1 mg As/L; 1 mg As/L; 10 mg As/L) for 10 days before mating and during gestation and the feeding period. Offspring were fed with the two different chows and exposed to different concentrations of arsenate in drinking water according to treatment of their mothers, up to two months of age. In the liver of newborn mice at two days of age, the exposure of pregnant mice had significant effects on the modulation of gene expression mainly in males, while in females some slight effects were observed in offspring from mothers exposed to the lowest As-concentration. For both sexes the deprived diet significantly modulates the hepatic gene expression. Major effects on the gene expression were observed in the liver of offspring whose exposure to arsenate in drinking water was continued for other two months after birth. The diet low in proteins affected the effects of As-exposure on gene expression and, at the same time, different concentrations of arsenate in drinking water caused different gene expression. These results suggest that physiological responses in tissues following semi-chronic exposure to arsenate are modulated not only by the levels of arsenic exposure, while differently influenced by host factors like age and gender. Furthermore, nutritional factors like the protein levels in the diet would significantly contribute to the overall toxic responses.