Mutagenesis, Vol. 16, No. 2, 163-168,
March 2001
© 2001 UK Environmental Mutagen Society/Oxford University Press
Induction and time-dependent accumulation of micronuclei in peripheral blood of transgenic p53+/– mice, Tg.AC (v-Ha-ras) and parental wild-type (C57BL/6 and FVB/N) mice exposed to benzene by inhalation
1 CIIT, Research Triangle Park, NC 27709, USA, Litron Laboratories, Rochester, NY 14620, USA and 2 National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
In this study, we determined the induction and time-dependent accumulation of micronuclei in the peripheral blood of transgenic C57BL/6 p53+/– mice (p53+/– mice), FVB/N Tg.AC v-Ha-ras mice (Tg.AC mice) and their isogenic parental strains, FVB/N and C57BL/6 following inhalation exposure to benzene. Our objective was to determine the impact of p53 heterozygosity in p53+/– mice and the v-Ha-ras transgene in Tg.AC mice on micronuclei induction following exposure to inhaled benzene. A flow cytometric technique that distinguishes micronucleated red blood cells (MN-RBC) from micronucleated reticulocytes (MN-RET) was used. Mice were exposed to 0, 100 or 200 p.p.m. benzene using three different exposure regimens that resulted in an equal weekly cumulative exposure (3000 p.p.m.xhours) to benezene: 100 p.p.m. for 6 h/day, 5 days/week, Monday to Friday (M–F); 100 p.p.m. for 10 h/day, 3 days/week, Monday, Wednesday, Friday (MWF); and 200 p.p.m. for 5 h/day, 3 days/week MWF. Significant elevations of MN-RBC and MN-RET were observed from 1 week exposure in all of the benzene-exposed groups that increased in a time-dependent manner for up to 13 weeks exposure. Fewer MN-RBC and MN-RET were induced in the 200 p.p.m. benzene exposure group than in mice exposed to 100 p.p.m. The reduction in the frequency of MN-RBC in the 200 p.p.m.x5 h benzene exposure group is probably due to metabolic saturation resulting in a lower bone marrow dose (concentrationxtime) than in the 100 p.p.m. exposure groups. No differences were observed in the frequency of MN-RBC or MN-RET in Tg.AC compared with the FVB/N isogenic controls. At certain time points the frequency of micronuclei was less in the heterozygous p53+/– mice than determined in the wild-type C57BL/6 isogenic parental strain. These results indicate that the heterozygous state in p53+/– mice, but not the v-Ha-ras transgene in Tg.AC mice can influence the induction of micronuclei by benzene.
3 To whom correspondence should be addressed at: CIIT, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA. Tel: +1 919 558 1329; Fax: +1 919 558 1300; Email: recio{at}ciit.org
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