ASSESSMENT OF 1,3-BUTADIENE MUTAGENICITY IN THE BONE-MARROW OF B6C3F1LACL TRANSGENIC MICE (BIG-BLUE(R)) - A REVIEW OF MUTATIONAL SPECTRUM AND LACL MUTANT FREQUENCY AFTER A 5-DAY 625 PPM 1,3-BUTADIENE EXPOSURE

1,3-Butadiene (BD) is a carcinogen that is bioactivated to at least tw o genotoxic metabolites. in the present article, we review briefly our previous studies an the in vivo mutagenicity and mutational spectra o f ED in bone marrow and extend these studies to examine the effect of exposure time (5-day vs. 4-week exposure to 625 ppm ED used in previou s studies) on the lacl mutant frequency in the bone marrow. Inhalation exposure to ED at 625 ppm and 1,250 ppm was mutagenic in vivo, induci ng an increase in the transgene mutant and mutation frequency in the b one marrow. Analysis of the mutational spectrum in ED-exposed and air control mice demonstrated that ED exposure induced an increased freque ncy of mutations at A:T base pairs. There was no difference in the loc i mutant Frequency determined in the bone marrow between a shore term exposure to ED (5 days) and a longer-term exposure (4 weeks). These da ta taken together demonstrate that inhalation exposure to ED induces i n vivo somatic cell mutation. (C) 1996 Wiley-Liss, Inc.