Abstract

Genetic risks resulting from exposure to mutagenic agents are often expressed in terms of an increase relative to the spontaneous load of genetic disease and malformation. This so-called doubling dose method rests on the assumption that induced mutations are similar in nature to those that arise spontaneously. In view of the fact that a sizable fraction of spontaneous mutations is associated with transposition of mobile elements, it is important to determine the response of these elements to mutagenic treatments. In these studies we examined the effects of X-rays and of formaldehyde on the excision of a mobile DNA sequence (P-element) from the genome of Drosophila, in the presence and absence of an MR chromosome, a second chromosome carrying 2 complete P-factors. The mutator activity of MR chromosomes is largely due to the transposition of these P-elements. The excision can be measured by the reversion of a mutation, causing singed bristles (resulting from a P-element insertion) to wild-type. In the radiation experiments, 20-h-old eggs were irradiated and in the chemical experiments, first-instar larvae were raised on formaldehyde-containing medium. The results indicate that (1) X-rays affect excision of the element directly, in the absence of MR whereas no effect was observed in the presence of MR, and (2) formaldehyde does not directly affect the excision, but is effective in decreasing the P-transposon-mediated excision. Concurrent experiments on sex-linked recessive lethals with or without MR and X-rays or formaldehyde were carried out. These data showed that the effect of formaldehyde on reversion of sn is small in comparison to its mutagenic effectiveness, as measured by the induction of recessive lethals.

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