A class of benzenoid chemicals suppresses apoptosis in C. elegans.
Benzene is a human carcinogen that might act through both genotoxic and nongenotoxic mechanisms to promote tumorigenesis. The genotoxic effects of benzene are well established, however, its potential nongenotoxic roles in carcinogenesis are poorly understood. We find that benzene suppresses somatic apoptosis in C. elegans; this suggests a potential nongenotoxic mechanism by which this chemical might promote tumorigenesis. We find that two other benzenoid chemicals, biphenyl and toluene, also inhibit apoptosis in C. elegans. Notably, these chemicals are suspected carcinogens in mammals; this suggests that a subclass of benzenoid chemicals might promote tumorigenesis by suppressing apoptosis. A benzene metabolite, 1,4-benzoquinone, can directly inhibit the activity of caspase-3; this suggests a general molecular mechanism by which benzenoid chemicals might suppress apoptosis. These findings suggest that C. elegans is an excellent alternative animal model for studying the antiapoptotic activity of tumor-promoting chemicals and for identifying in vivo targets of these chemicals.
Kokel
David
D
Department of MCD Biology, University of Colorado, Boulder, CO 80309, USA.
Xue
Ding
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001554:Benzene / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects*; D002273:Carcinogens / Q000494:pharmacology; D061945:Caspase Inhibitors; D020169:Caspases / Q000187:drug effects; D002452:Cell Count; D003510:Cyclohexanes / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009154:Mutation; D014050:Toluene / Q000494:pharmacology*
D001554:Benzene; D001555:Benzene Derivatives; D016227:Benzoquinones; D001713:Biphenyl Compounds; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D061945:Caspase Inhibitors; D020169:Caspases; D003510:Cyclohexanes; D014050:Toluene; C010574:biphenyl; C004532:quinone; C506365:Cyclohexane; C010219:mesitylene; C089223:ced-3 protein, C elegans; C042889:2-methyl-1,4-benzoquinone