MICRONUCLEI INDUCED IN PERIPHERAL-BLOOD OF E-MU-PIM-1 TRANSGENIC MICEBY CHRONIC ORAL TREATMENT WITH 2-ACETYLAMINOFLUORENE OR BENZENE BUT NOT WITH DIETHYL-NITROSAMINE OR 1,2-DICHLOROETHANE

Micronucleus induction in peripheral blood was examined during carcino genicity assays of the genotoxic carcinogens 2-acetylaminofluorene (2- AAF), benzene, diethylnitrosamine (DEN) and 1,2-dichloroethane (1,2-DC E) in lymphoma prone Emu-PIM-1 transgenic mice. In both sexes, micronu clei were increased in polychromatic (PCE) and normochromatic (NCE) er ythrocytes after 14 weeks of oral treatment with 75 mg/kg 2-AAF or 50 and 100 mg/kg benzene. The micronucleus frequencies induced by benzene were higher in males than in females. There was no apparent treatment related suppression of erythropoiesis by 2-AAF or by benzene. Blood m icronucleus frequencies induced by benzene were similar in transgenic mice and their non-transgenic litter mates. There was no micronucleus induction or PCE suppression detected in the blood of either sex after treatment with 1 and 3 mg/kg DEN or 100 to 300 mg/kg 1,2-DCE. At 40 w eeks bone marrow was sampled from mice given 100 mg/kg benzene, and it was confirmed that micronucleated PCE frequencies in blood were an ac curate reflection of those induced in bone marrow. However, the sponta neous and induced frequencies of micronucleated cells in blood were sl ightly higher in PCE than in NCE suggesting that a small degree of sel ective removal of micronucleated cells occurs in this mouse strain. Co ntrol micronucleus frequencies in Emu-PIM-1 mice appeared comparable t o those in other, non-transgenic mouse strains. Thus micronuclei are r eadily detectable in blood during chronic exposure to the bone-marrow clastogens 2-AAF and benzene, but not to DEN and 1,2-DCE, probably bec ause active species do not reach the bone marrow in sufficient concent rations to induce increases in micronuclei.