Ciranni R, Barale R, Adler I D
Dipartimento di Szienze dell'Ambiente e del Territorio, Università di Pisa, Italy.
Mutagenesis. 1991 Sep;6(5):417-21. doi: 10.1093/mutage/6.5.417.
Cancer hazard is due to genotoxic events in somatic cells and genetic hazard in the strict sense is due to mutagenic events in germ cells. The investigation of sensitivity differences between somatic and germinal cells is pertinent to the question whether a genotoxic carcinogen is also a germ cell mutagen. Cytogenetic damage induced by benzene in mice was evaluated by determining the frequencies of chromosomal aberrations in bone marrow and spermatogonial cells of male Swiss CD1 mice. First, the analysis was performed by administering 1 ml/kg (880 mg/kg) of benzene as a single oral dose and sampling either cell type after a wide range of times (6, 12, 18, 24, 30, 36, 42 and 48 h) to determine the time of maximum response. At this dose benzene showed high clastogenic activity in bone marrow cells with a peak between 24 and 30 h. In differentiating spermatogonia the frequency of aberrant cells was highest 24 h after treatment. The overall effect in spermatogonia was lower than in bone marrow cells. Second, the dose response was determined 24 h after treatment with two additional doses of benzene: 0.1 ml/kg (88 mg/kg) and 0.5 ml/kg (440 mg/kg) for bone marrow cells; 0.25 ml/kg (220 mg/kg) and 0.5 ml/kg (440 mg/kg) for differentiating spermatogonia. The clastogenic effect was dose dependent in both cell types. The frequencies of aberrant cells increased in a linear-quadratic manner in bone marrow and linearly in differentiating spermatogonia. Furthermore, the per cell damage was higher in bone marrow than in spermatogonial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
癌症风险源于体细胞中的基因毒性事件，而严格意义上的遗传风险则源于生殖细胞中的诱变事件。研究体细胞和生殖细胞之间的敏感性差异，对于确定一种基因毒性致癌物是否也是一种生殖细胞诱变剂这一问题具有重要意义。通过测定雄性瑞士CD1小鼠骨髓和精原细胞中的染色体畸变频率，评估了苯对小鼠的细胞遗传学损伤。首先，以1 ml/kg（880 mg/kg）的苯作为单次口服剂量进行给药，并在广泛的时间范围（6、12、18、24、30、36、42和48小时）后对任一细胞类型进行采样，以确定最大反应时间，从而进行分析。在此剂量下，苯在骨髓细胞中显示出高断裂活性，峰值出现在24至30小时之间。在分化中的精原细胞中，异常细胞的频率在处理后24小时最高。精原细胞中的总体效应低于骨髓细胞。其次，在另外两个苯剂量处理后24小时确定剂量反应：骨髓细胞分别为0.1 ml/kg（88 mg/kg）和0.5 ml/kg（440 mg/kg）；分化中的精原细胞分别为0.25 ml/kg（220 mg/kg）和0.5 ml/kg（440 mg/kg）。两种细胞类型中的断裂效应均呈剂量依赖性。骨髓中异常细胞的频率以线性 - 二次方式增加，而在分化中的精原细胞中呈线性增加。此外，骨髓中每个细胞的损伤高于精原细胞。（摘要截断于250字）
