Genetic toxicity of methamphetamine in vitro and in human abusers.
Methamphetamine (METH) is a widely abused psychomotor stimulant. Although numerous studies have examined METH-induced neurotoxicity, its ability to produce genotoxic effects has not been evaluated. In this article, we report on the genotoxicity of METH in vitro and in human METH abusers. METH induced his(+) revertants in Salmonella typhimurium strains TA98 and TA100, and increased the frequency of hprt mutants, micronuclei, and sister chromatid exchange (SCE) in cultured Chinese hamster ovary K1 (CHO-K1) cells. These METH-induced genotoxic effects were eliminated if METH exposure was conducted in the presence of rat liver S9, indicating that the genotoxicity was caused by METH, and not by metabolites of METH. In addition, reactive oxygen species (ROS) scavengers inhibited the METH-induced micronuclei in CHO-K1 cells. Further investigation with 76 human long-term METH abusers and 98 unexposed controls demonstrated that total METH exposure correlated with micronucleus and SCE frequencies in cultured lymphocytes. The results of this study indicate that METH is a genotoxic agent and that ROS may play a role in METH-induced genotoxicity.
Li
Jih-Heng
JH
National Bureau of Controlled Drugs, Department of Health, Taiwan, Republic of China. jhli@nbcd.gov.tw
Hu
Heng-Cheng
HC
Chen
Wei-Bang
WB
Lin
Shih-Ku
SK
D000328:Adult; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009154:Mutation; D051381:Rats; D017382:Reactive Oxygen Species; D012486:Salmonella typhimurium; D012854:Sister Chromatid Exchange; D019966:Substance-Related Disorders; D013997:Time Factors
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008694:Methamphetamine; D007041:Hypoxanthine Phosphoribosyltransferase