S-adenosylmethionine, S-adenosylhomocysteine and DNA methylation levels in the liver of rats fed methapyrilene and analogs.
The antihistamine methapyrilene (hydrochloride) and four close structural analogs, methaphenilene, methafurylene, thenyldiamine and clorothen, were given to rats at a concentration of 0.1% in drinking water for 34 weeks. Only methapyrilene produced notable histopathological changes in the liver, bile duct hyperplasia and focal cellular change. Methapyrilene produced an early and persistent elevation in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, which was 2.8 times the control levels at 34 weeks; none of the other antihistamines produced so high a ratio or altered the ratio as early. Methapyrilene, but not the other antihistamines, produced a significant increase in the methylation of liver DNA at 20 and 34 weeks, as measured by the level of 5-methyldeoxycytidine. The increase in deoxycytosine methylation is so far the only detected effect of the carcinogen methapyrilene on DNA which is absent in rats treated with its non-carcinogenic analogs.
Hernandez
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L
NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, Frederick, MD 21701.
Allen
P T
PT
Poirier
L A
LA
Lijinsky
W
W
D000631:Aminopyridines / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008701:Methapyrilene / Q000633:toxicity*; D008745:Methylation; D051381:Rats; D011916:Rats, Inbred F344; D012435:S-Adenosylhomocysteine / Q000032:analysis*; D012436:S-Adenosylmethionine / Q000032:analysis*
D000631:Aminopyridines; D002273:Carcinogens; D006710:Homocysteine; D003841:Deoxycytidine; D012436:S-Adenosylmethionine; D004247:DNA; D012435:S-Adenosylhomocysteine; D008701:Methapyrilene; C016569:5-methyldeoxycytidine