Genetic deletions at specific loci by polycyclic hydrocarbons in relation to carcinogenesis

✍ Scribed by O. G. Fahmy; Myrtle J. Fahmy

• Book ID: 102863426
• Publisher: John Wiley and Sons
• Year: 1970
• Tongue: French
• Weight: 778 KB
• Volume: 6
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910060212

✦ Synopsis

Abstract

The genetic properties of four benz[a]anthracene derivatives with varying carcinogenic potential were investigated on the stages of spermatogenesis in Drosophila melanogaster: two carcinogens, the 7,12‐dimethyl compound and its 7‐bromomethyl‐12‐methyl analogue; and two non‐carcinogens, methylated in the 1,7 or 3,9 positions. All proved virtually inactive with respect to the induction of point‐mutations: sex‐linked and autosomal recessive visibles and lethals. They were also ineffective in the production of chromosome breaks leading to major rearrangements, such as viable X‐fragments.

Specific mutability tests confirmed the inactivity of all compounds on representative loci within the euchromatin of the X‐chromosome. In contrast, they were active to various degrees in the deletion of those loci involved in the transcription of r‐RNA, as measured by the effect on the heterochromatic X‐nucleolar organizer region, yielding bobbed mutations. The carcinogenic derivatives induced a high frequency of these mutations, whereas the non‐carcinogens were virtually inactive. The compounds which were active on the nucleolar organizer were also effective on the Minute loci.

The mutagenic efficiency of the carcinogenic derivatives on the responsive loci proved to be differential, dependent on the chemical structure of the carcinogen and the metabolic activity of the target cells. The bearing of this phenomenon on specificity in carcinogenesis was discussed.