Differential effects of dehydroepiandrosterone and clofibrate on the binding of 7,12-dimethyl benz(a)anthracene to hepatic DNA in vivo--a preliminary study.
The effects of feeding two compounds, dehydroepiandrosterone (DHEA), an adrenal steroid, and clofibrate (CLOF) to rats (which are both hypolipidemic, hepatomegaly inducing and hepatic peroxisome proliferating agents) on the binding of 7,12-dimethylbenz(a)anthracene (DMBA) to hepatic DNA in vivo is compared. Male Sprague Dawley rats (two-three months old) were fed either DHEA or CLOF for 14 days at a dietary level of 0.8%. Control rats were pair fed. An increase in liver weight followed by increases per whole liver in total protein, without much change in DNA content was observed. Subsequently, all the animals were given a single intraperitoneal dose of [3H]DMBA (133 mumol/kg body weight, 102 microCi/rat) in 250 microliters dimethyl sulfoxide. Forty-eight hours later, binding of DMBA to hepatic DNA was determined. The results indicate that DMBA binding to DNA was reduced by 67% in DHEA-fed rats whereas in clofibrate-fed rats it was not significantly different from that of the controls.
Prasanna
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Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Hart
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Magee
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PN
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002994:Clofibrate / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
C032223:7,12-dimethylbenzanthracene-binding protein, rat; D002352:Carrier Proteins; D003687:Dehydroepiandrosterone; D004247:DNA; D002994:Clofibrate