Effect of short-term exposure of rats to dehydroepiandrosterone on the hepatic metabolism of dimethylnitrosamine.
The influence of short-term treatment with dehydroepiandrosterone (DHEA), a naturally occurring adrenal steroid, on hepatic metabolism and macromolecular interactions of the hepatocarcinogen dimethylnitrosamine (NDMA) was investigated in male Sprague-Dawley rats. Liver weight, total tissue protein (P less than 0.05), microsomal and cytosolic proteins and cytochrome P-450 (P less than 0.001) were all significantly increased in rats treated orally with DHEA (300 mg/kg body wt., suspended in 1.0 ml of sesame oil). The hepatic DNA content was not altered, however. Methylation of DNA by NDMA was reduced significantly in DHEA-treated rats (P less than 0.05). The binding of [14C]NDMA to hepatic proteins was greater in DHEA-treated rats. The results suggest that short-term treatment of rats with DHEA enhances the binding of NDMA-derived metabolites to hepatic proteins, resulting in the protection of DNA from the damaging effects of NDMA.
Prasanna
H R
HR
Fels Research Institute, Temple University School of Medicine, Philadelphia, PA 19140.
Hart
R W
RW
Magee
P N
PN
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009929:Organ Size; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D003687:Dehydroepiandrosterone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D004128:Dimethylnitrosamine