TOXICITY PROFILE OF BENZO[A]PYRENE IN THE MALE LACZ TRANSGENIC MOUSE (MUTAMOUSE) FOLLOWING ORAL-ADMINISTRATION FOR 5 CONSECUTIVE DAYS

The toxicity profile of benzo[a]pyrene (BP) was examined in the MutaMo use. The transgenic mouse integrated with lambda gt10 lacZ vectors is used worldwide as an experimental animal in in vivo mutagenesis testin g systems. There are few toxicity studies including carcinogenicity in the MutaMouse, and so far only a few carcinogenicity studies of BP ac companied with hematological and plasma biochemical examinations have been conducted even in generic mice. Accordingly, male mice were orall y administered BP at doses of 75 and 125 mg/kg/day for 5 consecutive d ays, and complete autopsy was conducted together with pathological, he matological, and plasma biochemical examinations and measurement of or gan weights 41 weeks after the last treatment. Squamous cell papilloma and hyperplasia in the forestomach were induced at incidences of 25 a nd 50%, respectively and were induced 26 weeks after the final treatme nt without any significant alterations in the hematological and plasma biochemical parameters in mice of the 125 mg/kg/day BP-treated satell ite group. Fourty-one weeks after the final treatments, 75 and 125 mg/ kg/day BP induced squamous cell carcinoma, papiloma, and hyperplasia i n the forestomach at incidences of 18 and 18%, 36 and 45%, and 91 and 91%, respectively, and anemia possibly due to continuous hemorrhage fr om tumors in the forestomach. BP (125 mg/kg/day) also produced maligna nt lymphoma with an incidence of 18%, accompanied by a marked increase in leukocyte count and decrease in erythrocyte count and by a remarka ble decrease in body weights 26 and 39 weeks after the last treatment. Moreover, administration of 75 and 125 mg/kg/day BP induced bronchiol ar-alveolar hyperplasia in the lung at incidences of 18 and 9%, respec tively. Slight increases were also observed in the weight of the liver and in the levels of urea nitrogen, creatinine, and potassium ion in the plasma biochemical examinations, although no significant pathologi cal alterations were found in the liver and kidney. This study provide s new information about BP toxicity including carcinogenicity in the M utaMouse developed for in vivo mutational analysis. (C) 1998 Academic Press.