Analysis of mutation frequencies following induction of epimutations by an environmental disruptor
Until recently, only genetic, nutritional and infectious agents were thought to cause adult onset diseases. Recent studies have now shown that factors other than these which include environmental agents such as Vinclozolin (an endocrine disruptor) can cause diseases in adults. Previous studies have shown that when a pregnant rat, at mid gestation period, is exposed to doses of Vinclozolin, the offspring shows disorders like sub fertility and spermatogenic defects. When these rats were allowed to age up to 10--14 months, they also gave rise to adult onset diseases like prostate disease, kidney diseases, tumor formations, immune abnormalities and so on. When the frequencies for the occurrence of the disease states were analyzed, it looked too improbable for genetic mutations to cause this number of diseases. So, it was thought that the disease phenotypes could be of an epigenetic origin. Heritable changes in epigenetic parameters like DNA methylation or histone modifications that can be passed on from one generation to the next without any change in the underlying DNA sequence are called epimutations. A change in epigenetic parameters could be passed on from one generation to the other. As a part of our study, we analyzed the mutation frequencies of F1 generation as well as F3 generation using the Big Blue Mutagenesis Assay system. We concluded that Vinclozolin causes an increase in mutation frequencies in the F3 generation. It does not act as a direct mutagen; it acts as an indirect mutagen. It causes changes in epigenetic parameters in the F1 generation and these changes in epigenetic parameters cause an increase in the spontaneous mutation frequencies of the F3 generation by acting as an indirect mutagen.