Toxicology of halogenated aliphatic hydrocarbons: Structural and molecular determinants for the disturbance of chromosome segregation and the induction of lipid peroxidation

被引:24
作者
Crebelli, R
Andreoli, C
Carere, A
Conti, L
Crochi, B
CottaRamusino, M
Benigni, R
机构
[1] Istituto Superiors di Sanita, Laboratory of Comparative Toxicology and Ecotoxicology, 00161 Rome, Viale Regina Elena
关键词
halogenated hydrocarbon; aneuploidy; structure-activity;
D O I
10.1016/0009-2797(95)03639-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:113 / 129
页数:17
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