Misregulation versus mutation in the alteration of gene expression by carcinogens through interactions with...

Carcinogens from different chemical series were tested on the wild-type allele of the complex white (w+) locus, which comprised some 5 recombinational subunits, the proximal part (w+4.5) exhibiting regulatory interactions with the neighbouring gene zeste (z). Three w+ loci were used, with different proximal regulatory sequences, including an unstable locus with a TE. Altered expression with each z w+ complex was assayed on the basis of the induction of aberrantly pigmented eye sectors known to be diagnostic of the interaction between z and the dosage of the functionally active w+4.5 subunits. All the tested carcinogens (DMN, DMBA and AFB1) were poorly active in the induction of the putative somatic deletions causing white (w-) eye sectors. In contrast, they were highly effective on the regulatory w+4.5 sequences in all test loci, as indicated by the significantly higher yield of red eye sectors (w-4.5) above the controls. However, this effect varied as a function of the chemical structure of the test compound and the genetic organisation of the regulatory targets. Germinal mutagenicity of the test compounds was assayed on X chromosomes carrying stable and unstable w+ loci, after the injection of adults and topical application on newly hatched larvae. Both techniques revealed that there was no association between the induction of somatic alterations in gene expression and the germinally induced mutations, including the TE w+4.5 deletions. Furthermore, the somatic events, unlike mutations, showed an association with the time of genetic determination during eye-disc cell differentiation. The present results were compatible with the concept of somatic gene misregulation by carcinogens.