Geonotoxicity study of illegal drug MDMA and its nitroso derivative N-MDMA by micronucleus and chromosomal aberration tests using Chinese hamsger lung fibroblast cell line
- 47 Downloads
An increase in incidence of the illegal use of tablets containing 3,4-methylenedioxymethamphetamine hydrochloride (MDMA) has recently become a widespread social problem. MDMA ingested orally reacts with nitrite in the stomach and is synthesized intoN-nitroso-3,4-methylenedioxymethamphetamine (N-MDMA). The aim of this study is to investigate the genotoxic effects of MDMA and N-MDMA on the basis of the results of an in vitro micronucleus (MN) test and an in vitro chromosomal aberration (CA) test using a Chinese hamster lung fibroblast cell line (CHL/IU).
Tablets containing MDMA obtained from the Regional Bureau of the Ministry of Health, Labor and Welfare were purified, and N-MDMA was synthesized from MDMA in our laboratory. To evaluate the effects of MDMA and N-MDMA, the MN test established by our laboratory and the CA test in accordance with the guidelines for toxicity studies of drugs recommended by the Ministry of Health, Labor and Welfare were performed.
In the MN test, no increased frequency of MNs was not found for MDMA. On the other hand, an apparently increased frequency of MNs was observed for N-MDMA. In the CA test, no CA was found for MDMA, but CA was observed for N-MDMA apparently.
N-MDMA genotoxicity was observed in the MN and CA tests. However, no MDMA genotoxicity was observed.
Key wordsMDMA N-MDMA genotoxicity micronucleus test chromosomal aberration test
- (1).NIDA-NIH-U.S. Department of Health & Human Services. MDMA (Ecstasy): NIDA INFO FACTS, March. 2005. p. 1–3.Google Scholar
- (2).National Police Agency, Government of Japan. White Paper on Police 2006. 2006. p. 158–165. (Article in Japanese)Google Scholar
- (3).World Health Organization. Expert Committee on Drug Dependence. Twenty-Second Report. 1985. p. 24–25.Google Scholar
- (6).Nishimura Y. Recent abuse of 3,4-methylenedioxymethamphetamine (“Yaoto-wang”, “Ecstasy”). Seishin Shinkeigaku Zasshi. 2002;104:819–833. (Article in Japanese)Google Scholar
- (14).Sofuni T (Ed). Data Book of Chromosomal Aberration Test in Vitro. Life-science Information Center; 1998. (Article in Japanese)Google Scholar
- (16).Ando H, Morita M. Possibility of in vitro and in vivo formations ofN-nitrosomethamphetamine. Reports of National Research Institute of Police Science. 1983;36:16–20. (Article in Japanese)Google Scholar
- (20).Li J, Suzuki Y, Shimizu H, Fukumoto M, Okonogi H, Nagashima T, et al. In vitro micronucleus assay of 30 chemicals in CHL cells. Jikeikai Med J. 1993;40:69–83.Google Scholar
- (22).Japanese Ministry of Health and Welfare. Guidelines for Toxicity Studies of Drugs. 1999.Google Scholar
- (27).Ishidate M Jr., Sofuni T, Yoshikawa K. Chromosomal aberration tests in vitro as a primary screening tool for environmental mutagenes and/or carcinogens. GANN Monograph on Cancer Research. 1981;27:95–108.Google Scholar
- (28).Sasaki MS. Chromosome Aberration Formation and Sister Chromatid Exchange in Relation to DNA Repair in Human Cells. Plenum Press; 1980, p. 285–314.Google Scholar