Dibenzo[a,l]pyrene induction of erythrocyte micronuclei in A/J and p53-deficient mice

Male A/J and C57B1/6 background p53(+/+), p53(+/-) and p53(-/-) mice were t reated with dibenzo[a,l]pyrene (DB[a,l]P), and micronucleus (MN) frequencie s were measured in erythrocytes from bone marrow and peripheral blood. MN w ere also evaluated with an antikinetochore antibody to distinguish whether they were derived from chromosome breakage or from chromosome missegregatio n. Treatment of A/J mice with 6 mg/kg DB [a,l]P, and harvest of marrow eryt hrocytes 48 and 72 hrs later, resulted in statistically significant increas es in kinetochore-negative MN levels (2.8x and 5.5x control levels, respect ively). Treatment of p53(+/+) and p53(-/-) mice with 18 mg/kg DB [a,l]P, an d harvest of marrow erythrocytes 48 hrs later, resulted in statistically si gnificant increases in kinetochore-negative MN frequencies (1.9x and 4.2x c ontrol levels, respectively). Our results indicate that DB[a,l]P induces mo derate levels of chromosome breakage without dose-dependence in erythrocyte s, and that p53 protein plays a protective role.