Hyperthermic modification of radiation induced gene conversion in Saccharomyces cerevisiae.

Effect of pre- and post-irradiation hyperthermia on the induction of gene conversion (non-reciprocal recombination) in diploid yeast cells was investigated. Post irradiation heat treatment does not significantly modify the frequency of gene conversion. Both low-level (51 degrees C-10 min) and lethal (51 degrees C, 40 min) pre irradiation heat treatments enhanced the gene conversion frequency by 17-49%. There was no quantitative correlation between the observed enhancement and the radiation dose. These results suggest that hyperthermia given prior to radiation not only sensitizes the cells to killing but also increases their convertogenic response. It has been suggested that recombination may be involved in carcinogenesis and tumour promotion. Based on these observations along with other reports, wherein hyperthermia was shown to modify the carcinogenic effects in animals as well as the genetic effects of radiation in vitro, it is possible to suggest that hyperthermia may have a potential to increase the second primary cancers, especially in long term survivors. Certain differences in the mechanism of interaction between radiation and heat in the pre- irradiation and post irradiation modalities appear likely.

Failure of exogenous methylated adenines to induce cytotoxic and genotoxic effects in yeast auxotrophic to adenine.

Alkylation of DNA is an important step in the biological efects of alkylating agents. In an attempt to determine the effect of alkylation at Ν 1 and Ν 3-positions in adenine, diploid yeast auxotrophic to adenine was cultured in synthetic medium in which adenine was replaced by Ν 1 or Ν 3-methyladenines. The expectation was that, the cells will incorporate methyladenines to the DNA newly synthesised by the salvage pathway and thus facilitate the expression of their biological effects, if any. The biological end points monitored were cell killing, gene conversion and reverse mutation. Contrary to expectation, no growth occurred in the cultures even after 48 h of incubation. The cells retained viability, but were only arrested in growth. When subcultured in the presence of sub-optimum levels of both adenine and Ν 1- methyladenine complete growth occurred. However, no enhancement in the induction of gene conversion or back mutation was observed in these cultures. Experiments with tritium labelled Ν 1-methyladenine showed that it is taken up by the cells. Hence, it is speculated that the ineffectiveness of methyladenines is due to their not being utilised as substrates in the synthesis of DNA by the salvage pathway. This is important for the assessment of the biological effects of DNA precursor pool alkylation.