Chemopreventive effects of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine against benzo[a]pyrene.
The putative antimutagenic/anticarcinogenic organosulfur compound, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC), has been demonstrated to inhibit the metabolic activation and the genotoxicity of N-nitrosodiethylamine. We have investigated the chemopreventive activity of AC-DDTC against benzo[a]pyrene (B[a]P) in the Salmonella typhimurium bacterial mutation assay, in the chromosome aberration assay using Chinese hamster lung fibroblast (CHL), and in the mouse micronucleus assay in bone marrow cells. In the bacterial mutation assay, AC-DDTC produced a concentration dependent decrease in the number of mutant colonies induced by B[a]P. The chromosome damaging responses of B[a]P in CHL cells were abolished by the treatment of AC-DDTC, approximately to the level of the control. In the in vivo mouse bone marrow micronucleus test, pretreatment of AC-DDTC 1 h prior to B[a]P reduced the frequency of micronucleated polychromatic erythrocytes. The inhibitory effects were statistically significant and dose-dependent. Our results demonstrate that AC-DDTC, one of the mixed disulfide model compounds of disulfiram, prevents the mutagenic effects of B[a]P.
Lee
B H
BH
Institute of Environment and Life Science, Hallym University, Chunchon, Kangwon-Do, South Korea. bhlee@wonnms.wonkwang.ac.kr
Lee
S
S
Kim
Y S
YS
Bertram
B
B
Wiessler
M
M
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001140:Aroclors / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D002869:Chromosome Aberrations; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D016587:Antimutagenic Agents; D001140:Aroclors; D002273:Carcinogens; D009153:Mutagens; C098444:S-(N,N-diethyldithiocarbamoyl)-N-acetylcysteine; D020111:Chlorodiphenyl (54% Chlorine); D001564:Benzo(a)pyrene; D000111:Acetylcysteine