Inhibition by diacylmethane derivatives of mutagenicity and nucleic acid binding of 2-aminofluorene derivatives.
The active methylene compounds acetylacetone, 1,1,1-trifluoroacetylacetone, benzoylacetone, dibenzoylmethane, and 1,3-indandione inhibited the mutagenicity of 2-nitrofluorene in Salmonella typhimurium. They also inhibited the N,O-acetyltransferase-catalyzed transfer RNA binding of N-hydroxy-2-acetylaminofluorene, but they did not inhibit N,O-acetyltransferase. However, only 1,3-indandione and 1,1,1-trifluoroacetylacetone significantly inhibited the binding of N-acetoxy-2-acetylaminofluorene to transfer RNA. Reaction of the trifluoro compound with the acetoxy compound yielded 1-(N-2-fluorenylacetamido)acetone. These results demonstrate that active methylene compounds can inhibit mutagenicity and nucleic acid binding of chemical carcinogens.
Wang
C Y
CY
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit, MI 48201.
Lee
M S
MS
Nagase
H
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Zukowski
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K
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D002074:Butanones / Q000494:pharmacology*; D047188:Chalcones; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005449:Fluorenes; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D007659:Ketones / Q000494:pharmacology*; D008297:Male; D009153:Mutagens / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009154:Mutation; D009696:Nucleic Acids / Q000378:metabolism*; D010422:Pentanones / Q000494:pharmacology*; D012343:RNA, Transfer / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000378:metabolism
D001565:Benzoates; D002074:Butanones; D047188:Chalcones; D005449:Fluorenes; D007189:Indans; D007192:Indenes; D007659:Ketones; D009153:Mutagens; D009696:Nucleic Acids; D010422:Pentanones; C019499:2-nitrofluorene; C061480:1,1,1-trifluoroacetylacetone; C008790:acetylacetone; C001445:1,3-indandione; D006881:Hydroxyacetylaminofluorene; D012343:RNA, Transfer; D015073:2-Acetylaminofluorene; C061481:dibenzoylmethane; D000123:Acetyltransferases; C035851:benzoylacetone