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GENETIC EFFECTS OF ENVIRONMENTAL CHEMICALS

Ziel

1) STUDY OF MOLECULAR INTERACTIONS OF ENVIRONMENTAL MUTAGENS AND CARCINOGENS AT DNA LEVEL.2) TO RELATE BIOLOGICAL CONSEQUENCES OF CHEMICAL MUTAGENS TO THE EXTENT AND SITE OF REACTION BETWEEN THE MUTAGENS AND DNA.4) DEVELOPMENT AND VALIDATION ASSAYS TO EVALUATE CHEMICALS CAPABLE OF INDUCING GENOMIC MUTATIONS.
Only 1 specific locus mutant was observed among the offspring of the experimental groups (a pink eyed mutation, 2 x 80 mg/kg ethylnitroso urea (ENU) group). However, a number of F1 offspring were recovered with a variegated coat colour phenotype. Genetic confirmation tests have shown these to be somatic and germinal mosaics for a newly occurring specific locus mutation with genotype (m/+,m/m*) where m is the test stock allele and m* is the newly occurring mutation at the particular locus.
1) THE MUTAGENECITY OF COMPOUNDS SELECTED BY THE APPROPRIATE CONTACT GROUP WILL BE TESTED BY THE SPECIFIC LOCUS ASSAY IN THE MOUSE. FOR ALL COMPOUNDS SELECTED, THE GERM CELL STAGE SPECIFICITY WILL BE TESTED AND THE SPECTRUM OF MUTATIONS AT THE SEVEN LOCI WILL BE COMPARED. COMPARING THESE QUALITATIVE RESULTS WITH THE RESULTS AS TO THE TYPE OF DNA ADDUCTS INDUCED MIGHT ALSO INDICATE IF CERTAIN DNA ADDUCTS LEAD ULTIMATELY TO PARTICULAR CLASSES OF MUTATION.

2) THE FOLLOWING TESTS WILL BE PERFORMED WITHIN THE PROJECT ON "GENOMIC MUTATIONS" :
I) HUMAN PERIPHERAL LYMPHOCYTES IN VITRO:
-CELL DIVISION FIDELITY, KARYOTYPE ANALYSIS IN MALE GERM CELLS.
II) MOUSE BONE MARROW IN VIVO:
-MICRONUCLEI; KARYOTYPE ANALYSIS IN MALE GERM CELLS.

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