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Micronucleus formation in mouse bone marrow cells in vivo in response to trans, trans-muconaldehyde
Y Oshiro1, P S Balwierz, G Witz
1Metabolism and Safety Evaluation, Pharmacia, 4901 Searle Parkway, Skokie, IL 60077, USA. yuki.oshiro@pharmacia.com
Abstract:
Benzene is a human leukemogen, and a bone marrow toxin and carcinogen in experimental animals. The reactive intermediates involved in benzene toxicity and their mechanism(s) of action have not been clearly delineated. We have investigated the clastogenic and cytotoxic effects of trans,trans-muconaldehyde (MUC), a reactive ring-opened benzene metabolite, in mouse bone marrow cells in vivo. Micronucleus formation was significantly increased when CD-1 mice were treated ip with MUC at 4 and 6 mg/kg/day for two days. These results suggest that leukemogenesis by benzene may be attributable, in part, to MUC-related clastogenic and cytotoxic effects in the bone marrow cells.

