Activation or detoxification of mutagenic and carcinogenic compounds in transgenic Drosophila expressing human glutathione S-transferase.
Sensitivity of transgenic Drosophila melanogaster with expression of a human gene encoding the glutathione S-transferase alpha subunit (GSTA1-1) to 1,2:5,6-dibenzanthracene (DBA) and 1,2-dichloroethane (DCE) was investigated in the somatic mutation and recombination test (SMART). We performed the same assay in control transgenic flies expressing the bacterial lacZ gene. Three types of transgenic Drosophila strains carrying GSTA1-1 were used: two transgenic strains homozygous for the second chromosome with a single-copy transgene insertion and one strain with two transgene insertions. Larvae carrying the lacZ gene were significantly more sensitive to genotoxic effects of DBA than those carrying three copies of the GSTA1-1 gene. The larvae with lacZ expression showed significantly lower sensitivity to DCE compared with those expressing GSTA1-1. Finally, a pretreatment with buthionine-sulphoximine (BSO) in experiment with DCE significantly decreased the frequency of mutation events in larvae with three GSTA1-1 copies in comparison with others.
Chroust
K
K
Department of Genetics and Molecular Biology, Masaryk University, Kotlarska 2, Brno, CZ-611 37, Czech Republic. chroust@sci.muni.cz
Jowett
T
T
Farid-Wajidi
M F
MF
Huang
J Y
JY
Ryskova
M
M
Wolf
R
R
Holoubek
I
I
D000818:Animals; D030801:Animals, Genetically Modified; D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000633:toxicity; D001711:Biotransformation / Q000187:drug effects / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D003433:Crosses, Genetic; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D005025:Ethylene Dichlorides / Q000378:metabolism / Q000633:toxicity; D005260:Female; D018628:Gene Dosage; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D015203:Reproducibility of Results; D019076:Transgenes; D014921:Wings, Animal / Q000187:drug effects; D001616:beta-Galactosidase / Q000235:genetics
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D005025:Ethylene Dichlorides; D007527:Isoenzymes; D009153:Mutagens; D019328:Buthionine Sulfoximine; C024565:ethylene dichloride; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D001616:beta-Galactosidase; C026486:1,2,5,6-dibenzanthracene