Carere A, Antoccia A, Cimini D, Crebelli R, Degrassi F, Leopardi P, Marcon F, Sgura A, Tanzarella C, Zijno A
Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy.
Environ Mol Mutagen. 1998;32(2):130-8.
Molecular cytogenetic methods were applied to investigate the effect of the occupational exposure to low concentrations of benzene and petroleum fuels on genomic stability. Twelve male gasoline station attendants (average benzene exposure of 0.32 mg/m3 as 8h TWA) and 12 age- and smoking-matched unexposed controls were selected for the study. The incidence of hyperploidy and polyploidy in peripheral lymphocytes was evaluated through in situ hybridization of interphase cells, harvested 24 hr after stimulation, with centromeric probes of chromosomes 7, 11, 18, and X. For half of the subjects, metaphases harvested 24 hr later were analyzed. The incidence of chromosome loss in vitro was determined in cytokinesis-blocked cells, harvested at 66 hr, through the hybridization of micronuclei with a pancentromeric probe. Ten thousand chromosomes (more than 200 metaphases equivalent) and 2,000 binucleated cells/person were scored for hyperploidy and micronucleus analysis, respectively. The results obtained did not show any exposure-related excess of hyperploidy or micronucleus formation. Conversely, the age of the subjects was significantly correlated with several markers of genomic instability, such as the incidence of chromosome X and chromosome 18 hyperploidy, total hyperploidy and polyploidy, and close to statistical significance with chromosome loss. Smoking habits did not appear to contribute significantly to the effects measured. The parallel analysis of hyperploidy and polyploidy in interphase nuclei in 24-hr cultures and in metaphase cells harvested 24 hr later showed basically similar incidences of aneuploid cells, indicating that no significant selection against hyperploid and polyploid types occurred during the first cell cycle in vitro.
应用分子细胞遗传学方法研究职业性接触低浓度苯和石油燃料对基因组稳定性的影响。选取12名男性加油站工作人员(8小时时间加权平均苯暴露量为0.32毫克/立方米)和12名年龄及吸烟情况相匹配的未暴露对照者进行研究。通过对刺激后24小时采集的间期细胞与7号、11号、18号染色体及X染色体的着丝粒探针进行原位杂交,评估外周血淋巴细胞中超倍体和多倍体的发生率。对一半受试者,分析24小时后采集的中期细胞。通过微核与全着丝粒探针杂交,在66小时采集的胞质分裂阻断细胞中测定体外染色体丢失的发生率。分别对一万条染色体(相当于200多个中期细胞)和每人2000个双核细胞进行超倍体和微核分析评分。所得结果未显示出与暴露相关的超倍体或微核形成增加。相反,受试者年龄与基因组不稳定的几个标志物显著相关,如X染色体和18号染色体超倍体发生率、总超倍体和多倍体发生率,且与染色体丢失接近统计学显著相关。吸烟习惯似乎对所测效应无显著影响。对24小时培养的间期核及24小时后采集的中期细胞中的超倍体和多倍体进行平行分析,结果显示非整倍体细胞发生率基本相似,表明在体外第一个细胞周期中未发生针对超倍体和多倍体类型的显著选择。