Inhibition by diacylmethane derivatives of mutagenicity in Salmonella typhimurium and tRNA-binding of chemical carcinogens.
Effects of diacylmethanes on the mutagenicity of 2-naphthohydroxamic acid, methylnitrosourea, benzo[a]pyrene and aflatoxin B1 in S. typhimurium and the tRNA binding by benzo[a]pyrene and aflatoxin B1 were investigated. Acetylacetone, benzoylacetone and dibenzoylmethane inhibited the mutagenicity of 2-naphthohydroxamic acid, and dibenzoylmethane and 1,3-indandione inhibited that of methylnitrosourea, benzo[a]pyrene and aflatoxin B1. The binding to tRNA of benzo[a]pyrene and aflatoxin B1 was inhibited by benzoylacetone and dibenzoylmethane, and dibenzoylmethane, 1,3-indandione and 1,1,1-trifluoroacetylacetone, respectively. The inhibition of methylnitrosourea mutagenicity was observed when the bacteria were exposed concomitantly to the inhibitors and the mutagen, but not when they were exposed to the inhibitors 1 h after exposure to the mutagen. These results demonstrate that active methylene compounds can inhibit mutagenicity and nucleic acid-binding of chemical carcinogens presumably by trapping carcinogenic electrophiles, and they are potential anti-carcinogenic agents during the initiation stage.
Wang
C Y
CY
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Lee
M S
MS
Zukowski
K
K
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000037:antagonists & inhibitors; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors; D001565:Benzoates / Q000633:toxicity; D002074:Butanones / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D047188:Chalcones; D004305:Dose-Response Relationship, Drug; D006898:Hydroxylamines / Q000037:antagonists & inhibitors; D007189:Indans / Q000633:toxicity; D008697:Methane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D009153:Mutagens / Q000037:antagonists & inhibitors*; D010422:Pentanones / Q000633:toxicity
D000348:Aflatoxins; D001565:Benzoates; D002074:Butanones; D002273:Carcinogens; D047188:Chalcones; D006898:Hydroxylamines; D007189:Indans; D009153:Mutagens; D010422:Pentanones; C020423:N,N-naphthaloylhydroxylamine; D001564:Benzo(a)pyrene; C061480:1,1,1-trifluoroacetylacetone; C008790:acetylacetone; C001445:1,3-indandione; D008770:Methylnitrosourea; D016604:Aflatoxin B1; C061481:dibenzoylmethane; C035851:benzoylacetone; D008697:Methane