PROTEIN VARIABILITY IN MALE AND FEMALE WISTAR RAT-LIVER PROTEINS

In the emerging field of mechanistic toxicology, growing attention is being paid to the interpretation of sex-related toxic responses. The W istar rat outbred stock is a frequently used rodent for toxicity testi ng. Outbred strains, which display a relatively high degree of genetic variability between the individual animals are often used in risk ass essment, as they are considered to best approximate the variability pr esent in a human population. In this study two-dimensional (2-D) prote in gel electrophoresis was applied to investigate the liver protein pa tterns of male and female Wistar rats and to search for (i) sex-relate d and (ii) interindividual qualitative and quantitative differences in protein expression. Among the sexes, six proteins were detected that were shown to be exclusively present in male rats and one that was pre sent only in females. A male-specific protein was tentatively assigned to alpha(2u), globulin. Seven protein spots showed statistically sign ificant abundance changes (p < 0.001). between males and females, one was tentatively assigned to heme oxygenase 1 and another to the 23 kDa morphin-binding protein. Four sets of protein spots were detected tha t showed positional shifts in the individual patterns and are likely t o represent polymorphic proteins inherent in the Wistar rat. These res ults form a valuable basis for future investigations of drug-induced c hanges in the male and female Wistar rat liver pattern.