Evidence for translational control of the binding of 7, 12-dimethylbenz[a]anthracene to DNA of murine epidermal cell in culture.
The effects of various inhibitors of aryl hydrocarbon hydroxylase (AHH), antioxidants, inhibitors of DNA, RNA, and protein synthesis, and protease inhibitors on the binding of [7,12-3H]dimethylbenz[a]anthracene ([3H] DMBA) to DNA of murine epidermal cells in culture have been investigated. 7,8-Benzoflavone, 5,6-benzoflavone and methyrapone (inhibitors of AAH) and antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), efficiently reduced the binding of [3H] DMBA to cellular DNA. Inhibitors of DNA and RNA synthesis did not affect this process whereas inhibitors of protein synthesis suppressed the binding of [3H] DMBA to cellular DNA. Protease inhibitors p-tosylamide-2-phenylchloromethyl ketone (TPCK) and p-tosyl-L-lysine chloromethyl ketone (TLCK) also reduced the interaction between DMBA and DNA. Thus, it appears that binding of DMBA to cellular DNA is regulated at the level of translation or/and post translation.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D051379:Mice; D011480:Protease Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*
D000963:Antimetabolites; D001551:Benz(a)Anthracenes; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases