Genotoxicity of tauromustine, a new water soluble taurine-based nitrosourea. I. Mutagenic and clastogenic activity of tauromustine in vitro.
Tauromustine (TCNU) a new taurine-based nitrosourea in phase III clinical trials against colon cancer, has been tested and compared with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (CCNU) for mutagenic potential in Salmonella typhimurium TA98 and TA100 and, for its ability to cause chromosome aberrations and sister chromatid exchanges (SCE) in human lymphocytes. A dose dependent increase in the number of mutations in S. typhimurium TA100 but not in TA98 was found from 1.6 to 1000 micrograms/plate for both TCNU and CCNU. In addition, in the presence of Aroclor activated liver microsomes, CCNU caused a further increase in the mutation frequency which was not found for TCNU. A dose dependent increase in the chromosome aberration rate in human lymphocytes was induced by both TCNU and CCNU at concentrations ranging from 3.75 to 30 micrograms/ml after 24 h treatment during the last cell cycle. When lymphocytes were treated in G0 both TCNU and CCNU induced a higher frequency of aberrations at 15 and 30 micrograms/ml than during the last cell cycle and, unexpectedly, chromosome-type, i.e. dicentrics appeared. The difference in the frequency of aberrations in these two phases may be related to the different levels of O6-methyl guanine transferase present in resting contra cycling lymphocytes. TCNU at 0.8-8 micrograms/ml also induced a dose dependent increase in the number of SCE in human lymphocytes. Neither the number of chromosomal aberrations nor the number of SCE were affected by the addition of 1000 micrograms/ml taurine to the culture medium.
Hartley-Asp
B
B
Kabi Pharmacia Oncology, Lund, Sweden.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002869:Chromosome Aberrations; D006801:Humans; D066298:In Vitro Techniques; D008130:Lomustine / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D009153:Mutagens; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea; D008130:Lomustine