DEMONSTRATION OF BENZO(A)PYRENE-INDUCED DNA-DAMAGE IN MICE BY ALKALINE SINGLE-CELL GEL-ELECTROPHORESIS - EVIDENCE FOR STRAND BREAKS IN LIVER BUT NOT IN LYMPHOCYTES AND BONE-MARROW

Alkaline single cell gel electrophoresis (also known as the 'comet ass ay') was used to measure DNA strand breaks and alkali-labile sites in peripheral lymphocytes, bone marrow and liver cells of C57BL/6 mice or ally exposed to benzo(a)pyrene. Although this polycyclic aromatic hydr ocarbon is a well-known genotoxic agent, little is known about to what extent it actually induces DNA strand breaks in peripheral lymphocyte s and other tissues after in vivo exposure. Significant and dose-relat ed damage was observed in liver cells after three days of exposure (lo west observed effect level being 3x100 mg benzo(a)pyrene/kg b.wt.). No such damage could be observed in the lymphocytes and bone marrow cell s even after administration of 3x150 mg benzo(a)pyrene/kg b.wt. The re ference substance cyclophosphamide produced pronounced DNA damage in l ymphocytes and bone marrow cells already in a single dose of 100 mg/kg b.wt. The present mouse study questions the usability of DNA strand b reaks in peripheral lymphocytes as an indicator of benzo(a)pyrene-indu ced genotoxicity.