METHYL TERTIARY BUTYL ETHER LACKS TUMOR-PROMOTING ACTIVITY IN N-NITROSODIETHYLAMINE-INITIATED B6C3F1 FEMALE MOUSE-LIVER

Methyl tertiary butyl ether (MTBE) is an additive in some formulations of unleaded gasoline (UG) that enhances octane and reduces carbon mon oxide emissions from motor vehicles, MTBE in CD-1 mice and UG in B6C3F 1 mice increased the incidence of liver tumors selectively in female m ice in their chronic bioassays, Both agents were negative in in vitro tests of genotoxicity, and exhibit similar hepatic microsomal cytochro me P450 activity and hepatocyte proliferation after short-term exposur e, We previously demonstrated that UG has hepatic tumor-promoting acti vity in DEN-initiated female B6C3F1 mice, Thus, we hypothesized that M TBE would have hepatic tumor-promoting activity in the same initiation -promotion model system in which UG was a hepatic tumor promoter, Twel ve-day-old female B6C3F1 mice were initiated with a single i.p. inject ion of the mutagen N-nitrosodiethylamine (DEN) (5 mg DEN/kg, 7.1 ml/kg body weight) or saline, Beginning at 8 weeks of age, mice were expose d to 0 ppm or the hepatocarcinogenic dose of approximately 8000 ppm MT BE. After subchronic exposure, MTBE significantly increased liver weig ht and hepatic microsomal cytochrome P450 activity without hepatotoxic ity or an increase in non-focal hepatocyte DNA synthesis, These are su bchronic effects similar to those produced by UG, However, MTBE did no t significantly increase the mean size of hepatic foci and volume frac tion of the liver occupied by foci as compared to DEN-initiated contro ls at either 16 or 32 weeks, The lack of tumor-promoting ability of MT BE in DEN-initiated female mouse liver was unexpected and suggests tha t MTBE does not produce liver tumors through a tumor-promoting mechani sm similar to that of UG.