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.
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.
复制标题
通过吸入苯暴露的转基因 p53/- 小鼠、Tg.AC (v-Ha-ras) 和亲代野生型 (C57BL/6 和 FVB/N) 小鼠外周血中微核的诱导和时间依赖性积累。
DOI：
10.1093/mutage/16.2.163
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发表时间：
2001
期刊：
影响因子：
2.7
通讯作者：
Recio,L
中科院分区：
文献类型：
--
作者：
Healy,LN;Pluta,LJ;James,RA;Janszen,DB;Torous,D;French,JE;Recio,L
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-rasmice (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-rastransgene 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.×hours) 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.×5 h benzene exposure group is probably due to metabolic saturation resulting in a lower bone marrow dose (concentration×time) 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-rastransgene in Tg.AC mice can influence the induction of micronuclei by benzene.
