Dibenzo[a,l]Pyrene Induction of Erythrocyte Micronuclei in A/J and P53-Deficient Mice

Abstract

Male A/J and C57Bl/6 background p53^+/+, p53^+/- and p53^−/- mice were treated with dibenzo[a,l]pyrene (DB[a,l]P), and micronucleus (MN) frequencies were measured in erythrocytes from bone marrow and peripheral blood. MN were also evaluated with an antikinetochore antibody to distinguish whether they were derived from chromosome breakage or from chromosome missegregation. Treatment of A/J mice with 6 mg/kg DB[a,l]P, and harvest of marrow erythrocytes 48 and 72 hrs later, resulted in statistically significant increases in kinetochore-negative MN levels (2.8x and 5.5x control levels, respectively). Treatment of p53^+/+ and p53^−/- mice with 18 mg/kg DB[a,l]P, and harvest of marrow erythrocytes 48 hrs later, resulted in statistically significant increases in kinetochore-negative MN frequencies (1.9x and 4.2x control levels, respectively). Our results indicate that DB[a,l]P induces moderate levels of chromosome breakage without dose-dependence in erythrocytes, and that p53 protein plays a protective role.

Key Words:

• dibenzo[a,l]pyrene
• mouse
• erythrocyte
• micronucleus