Changes of SCE frequency and chromatin molecular composition in rat progeny whose mothers were treated with oral contraceptives in early pregnancy

Abstract

Wistar female rats were fed with oral contraceptives (OC, containing ethinylestradiolum and metyl-norethrindronum) in early pregnancy. The dosage used for rats was 6.6 times more than the clinical dosage for humans in weight per kilogram. The SCE frequencies of liver and ovary cells and the changes of chromatin molecular composition in progeny of the rats fed with OC were observed. The results showed that the liver and ovary cells of newborns 12 h after birth exhibited increased SCEs value (liver: p<0.03; ovary: p<0.0004). These elevated SCE frequencies declined to the normal level about the 15th day after birth. The results for the quantity of nonhistone (NHP) and chromatin RNA in mother rats and their progenies also exhibited a significant increases, and declined to the normal level at the same period mentioned above. The results suggested that the high level of NHP and chromatin RNA may be induced by OC fed in early pregnancy and the maintained for some time after withdrawal of the OC pills. The changes of the chromatin molecular composition are perhaps somehow related to the increased SCE frequencies in the rat-liver cells. We suggest that the external steroids and their metabolites may activate more genes which were originally inactivea and result in increased junctions between euchromatin and heterochromatin, resulting in more SCEs in quickly dividing embryo cells. The report here suggests that during early pregnancy the pills taken by women following CO failures may have a potential mutagenic effect on their progeny for some time after the pills have been stopped.