Induction of chromosome malsegregation by halogenated organic solvents in Aspergillus nidulans: unspecific or specific mechanism?

Three chloromethanes (dichloromethane, chloroform and carbon tetrachloride) and 8 chlorinated ethanes (1,1- and 1,2-dichloroethane, 1,1,1- and 1,1,2-trichloroethane, 1,1,1,2- and 1,1,2,2-tetrachloroethane, pentachloroethane and hexachloroethane) were assayed in tests for the induction of mitotic segregation in Aspergillus nidulans diploid strain P1. Eight of the 11 compounds assayed (dichloromethane, chloroform, carbon tetrachloride, 1,1- and 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,1,2- and 1,1,2,2-tetrachloroethane) significantly increased the frequency of morphologically abnormal colonies which produced euploid whole-chromosome segregants (haploids and non-disjunctional diploids). Only in one case (1,1,1,2-tetrachloroethane) was a borderline increase in crossing-over frequency observed, thus suggesting the involvement of non-DNA targets in aneuploidy induction by these chlorinated hydrocarbons. Conclusive evidence for the induction of aneuploidy as the primary genetic event was provided by experiments in haploid strain 35 with 1,2-dichloroethane and 1,1,1,2-tetrachloroethane. Mutagenic, lethal and growth-arresting activities were quantitatively estimated and compared to a series of descriptors of physical and chemical properties of the molecules by means of multivariate statistical analysis. Lipophilicity, known to be related to c-mitotic activity, did not show any significant relationship with aneuploidizing activity, whereas a possible correlation among physico-chemical descriptors and toxic properties of test chemicals was highlighted.