In vitro/in vivo effects of Mesna on the genotoxicity and toxicity of cyclophosphamide--a study aimed at clarifying the mechanism of Mesna's anticarcinogenic activity.
Cyclophosphamide is an effective antitumor agent with considerable side effects such as urotoxicity and carcinogenicity. These negative attributes may be caused by toxic and genotoxic metabolites, respectively. Mesna (sodium 2-mercaptoethane sulfonate) decreases the urotoxicity by scavenging the toxic metabolite acrolein. The present study was aimed at elucidating whether a similar scavenging of genotoxic alkylating intermediates could be found, which might cause the reduction in carcinogenicity. In vitro studies on the genotoxic and toxic properties of cyclophosphamide and its major metabolites to bacteria were therefore performed in the presence of Mesna. Mesna did not reduce the mutagenicity of any of the tested metabolites. Mesna clearly inhibited the toxic properties of acrolein. After in vivo application of Mesna and cyclophosphamide to rats, however, a lower yield of mutagens in the excreted urine was observed than after application of cyclophosphamide only.
D000171:Acrolein / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001711:Biotransformation; D003520:Cyclophosphamide / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008623:Mercaptoethanol / Q000031:analogs & derivatives*; D015080:Mesna / Q000494:pharmacology*; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D009153:Mutagens; D008623:Mercaptoethanol; D000171:Acrolein; D003520:Cyclophosphamide; D015080:Mesna