Genotoxicity of ethyl carbamate (urethane) in Salmonella, yeast and human lymphoblastoid cells.
Ethyl carbamate is a known carcinogen occurring in fermented food and beverages and is therefore of interest for food safety assurance. We studied the genotoxicity of ethyl carbamate in Salmonella typhimurium, in Saccharomyces cerevisiae and in human lymphoblastoid TK6 cells. In absence of cytochrome P450 enzymes, no ethyl carbamate-mediated genotoxicity was observed in any of the three test systems in the non-cytotoxic range. In the presence of an activating system, ethyl carbamate was found to be mutagenic in Salmonella typhimurium strain TA100 but not in strains TA98 and TA102, indicating base-pair substitutions at G-C base pairs. In contrast, no significant mutagenicity of ethyl carbamate could be detected in human lymphoblastoid TK6 cells. However, applied in cytotoxic concentrations, ethyl carbamate was genotoxic for Saccharomyces cerevisiae in the absence of P450-mediated metabolic activation. Inhibitors of P450IIE1 (DMSO, ethanol and dithiodiethylcarbamate) diminished ethyl carbamate-mediated mutagenicity in Salmonella typhimurium strain TA100 in a dose dependent manner, suggesting that P450IIE1 is the activating enzyme.
Hübner
P
P
Laboratory for Food Chemistry, University of Bern, Switzerland.
Groux
P M
PM
Weibel
B
B
Sengstag
C
C
Horlbeck
J
J
Leong-Morgenthaler
P M
PM
Lüthy
J
J
D000970:Antineoplastic Agents / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D009152:Mutagenicity Tests; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D012475:Salmonella / Q000187:drug effects / Q000235:genetics*; D014520:Urethane / Q000633:toxicity*
D000970:Antineoplastic Agents; D002273:Carcinogens; D014520:Urethane; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2