Micronuclei induced in peripheral blood of E mu-PIM-1 transgenic mice by 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 carcinogenicity assays of the genotoxic carcinogens 2-acetylaminofluorene (2-AAF), benzene, diethylnitrosamine (DEN) and 1,2-dichloroethane (1,2-DCE) in lymphoma prone E mu-PIM-1 transgenic mice. In both sexes, micronuclei were increased in polychromatic (PCE) and normochromatic (NCE) erythrocytes 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 micronucleus 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 weeks bone marrow was sampled from mice given 100 mg/kg benzene, and it was confirmed that micronucleated PCE frequencies in blood were an accurate reflection of those induced in bone marrow. However, the spontaneous and induced frequencies of micronucleated cells in blood were slightly higher in PCE than in NCE suggesting that a small degree of selective removal of micronucleated cells occurs in this mouse strain. Control micronucleus frequencies in E mu-PIM-1 mice appeared comparable to those in other, non-transgenic mouse strains. Thus micronuclei are readily detectable in blood during chronic exposure to the bone-marrow clastogens 2-AAF and benzene, but not to DEN and 1,2-DCE, probably because active species do not reach the bone marrow in sufficient concentrations to induce increases in micronuclei.
Armstrong
M J
MJ
Merck Research Laboratories, West Point, PA 19406.
Galloway
S M
SM
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001554:Benzene / Q000633:toxicity*; D002869:Chromosome Aberrations; D004052:Diethylnitrosamine / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015162:Micronucleus Tests; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1; D013997:Time Factors
D005025:Ethylene Dichlorides; D011518:Proto-Oncogene Proteins; D004052:Diethylnitrosamine; C024565:ethylene dichloride; D015073:2-Acetylaminofluorene; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1; D001554:Benzene