Crebelli R, Andreoli C, Carere A, Conti L, Crochi B, Cotta-Ramusino M, Benigni R
Istituto Superiore di Sanita, Laboratory of Comparative Toxicology and Ecotoxicology, Rome, Italy.
Chem Biol Interact. 1995 Nov 17;98(2):113-29. doi: 10.1016/0009-2797(95)03639-3.
The induction of mitotic chromosome malsegregation, mitotic arrest and lethality by a set of 55 halogenated hydrocarbons was investigated. To this aim, genetic assays in the mould Aspergillus nidulans, able to provide precise quantitative information on the end-points studied, were used throughout the work. The experimental data obtained were used to develop QSAR models for the induction of aneuploidy, which pointed to a major role of electrophilicity as molecular determinant for the aneugenic potential of the halogenated hydrocarbons investigated. Within the hypothesis of a link between the electrophilicity of haloalkanes and their propensity to undergo a reductive biotransformation, with production of free radical species, a subset of 27 compounds was also tested for the ability to induce lipid peroxidation in rat liver microsomes in vitro. The results obtained indicate a partial coincidence between the abilities to initiate lipid peroxidation and to disturb chromosome segregation at mitosis. The data base obtained was also used to investigate the relationship between chemical structure and peroxidative potential. The analysis indicated that electronic and structural parameters related to the ease of homolitic cleavage of the carbon-halogen bond play a pivotal role as determinants for the peroxidative character of haloalkanes.
研究了一组55种卤代烃对有丝分裂染色体错分离、有丝分裂停滞和致死性的诱导作用。为此，在整个研究过程中使用了构巢曲霉中的遗传分析方法，该方法能够提供有关所研究终点的精确量化信息。获得的实验数据用于建立非整倍体诱导的QSAR模型，该模型指出亲电性作为所研究卤代烃非整倍体潜力的分子决定因素起着主要作用。在卤代烷的亲电性与其进行还原性生物转化并产生自由基物种的倾向之间存在联系的假设下，还测试了27种化合物在体外诱导大鼠肝微粒体脂质过氧化的能力。所得结果表明引发脂质过氧化的能力与在有丝分裂时干扰染色体分离的能力之间存在部分重合。所获得的数据库还用于研究化学结构与过氧化潜力之间的关系。分析表明，与碳 - 卤键均裂难易程度相关的电子和结构参数作为卤代烷过氧化特性的决定因素起着关键作用。
