Characterization of the genotoxic action of three structurally related 1,2-dihaloalkanes in Drosophila melanogaster.
The genetic activity profiles of three structurally related dihaloalkanes, 1,2-dibromoethane (DBE), 1,2-dichloroethane (DCE) and 1-bromo-2-chloroethane (BCE), were compared in germ cells and somatic tissue of Drosophila melanogaster. The two genotoxicity indices estimated after mutagen exposure of male germ cells were (i) the hypermutability index fexr-/fexr+, measured by the increased frequency of induced recessive lethals (RL) in a strain defective in DNA excision repair (exr-), as compared to the wild type (exr+); (ii) the relative clastogenicity index CL/RL, expressed by the ratio of chromosomal aberrations (CL; ring-X loss) to RL determined in exr+ strains. The fexr-/fexr+ index for DBE was 4-5 times higher than those for DCE and BCE, suggesting a difference in the types of premutagenic lesions produced by DBE in comparison to DCE and BCE. The relative clastogenicity indices for BCE (CL/RL = 0.29) and DCE (0.41) are similar to the value of 0.37 estimated for DBE in an earlier study, all indicating that the three compounds or their metabolites are incapable of forming DNA crosslinks. In somatic cells, after inhalation treatment of female larvae, the effectiveness for the induction of interchromosomal recombination decreased in the order BCE > or = DBE > DCE. It is concluded that in accordance with other studies also in Drosophila the glutathione-mediated pathway is the major cause of genotoxicity caused by DBE, DCE and BCE.
Ballering
L A
LA
Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratories, Leiden, Netherlands.
Nivard
M J
MJ
Vogel
E W
EW
D000818:Animals; D001711:Biotransformation; D004331:Drosophila melanogaster / Q000187:drug effects; D004980:Ethane / Q000031:analogs & derivatives* / Q000633:toxicity; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005260:Female; D005854:Germ Cells / Q000187:drug effects; D006579:Heterozygote; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D011995:Recombination, Genetic / Q000187:drug effects; D013329:Structure-Activity Relationship
D005025:Ethylene Dichlorides; D006842:Hydrocarbons, Brominated; D006846:Hydrocarbons, Halogenated; D009153:Mutagens; C024565:ethylene dichloride; C039590:1-bromo-2-chloroethane; D004980:Ethane; C027947:methylene bromide