Effects of caffeine on the frequencies of chromosomal aberrations and sister-chromatid exchanges induced by mutagenic agents in root tips of Vicia faba

270 203 Sturelid, S., and B.A. Kihlman, Department of Genetics and Plant Breeding, Royal Agricultural College of Sweden, S-750 07 Uppsala 7 (Sweden) Effects of caffeine on the frequencies of chromosomal aberrations and sisterchromatid exchanges induced by mutagenic agents in root tips of Vicia faba The possible relationships between post-replication repair (PRR), sisterchromatid exchanges (SCEs) and chromosomal aberrations (ChA's) have been studied in cytological experiments with the aid of caffeine, an inhibitor of the gap-filling step of PRR. In one series of experiments we analyzed the effect of caffeine on the frequencies of ChA's and SCEs obtained after exposure to various mutagenic agents. SCEs were visualized by the fluorescent-plus-Giemsa technique. In another series of experiments we studied how the caffeine potentiation of the frequency of ChA's induced by various mutagenic agents was influenced by the temperature during the 5-h post-treatment exposure of caffeine. The following observations were made: (1) post-treatments with caffeine enhanced not only the frequency of ChA's produced by agents with Sdependent effects (maleic hydrazide, azaserine and a number of mono-, di- and tri-functional alkylating agents), but also that produced by X-rays in G2 and by bleomycin in S and G2, (2) for all di- and tri-functional alkylating agents studied, as well as for monofunctional quinacrine mustard, methylnitrosourea, methylnitronitrosoguanidine and ethyl methanesulphonate, post-treatments with caffeine caused a strong enhancement of the induced frequency of ChA's only at temperatures close to those optimal for growth; in contrast, the frequency of ChA's produced by the monofunctional alkylating agents methyl methanesulphonate and dimethylsulphate, as well as that produced by azaserine and maleic hydrazide, were enhanced by caffeine independently of the temperature during the 5-h post-treatment exposure to caffeine, (3) the frequency of SCEs was increased by X-rays and by bleomycin in cells exposed during G1 and S, but only at doses that also produced high frequencies of ChA's, (4) all the alkylating agents tested strongly increased the frequencies of SCEs at concentrations lower than those required for the production of ChA's, and (5) post-treatments with caffeine, which strongly increased the frequency of ChA's produced by mono-, di- and tri-functional alkylating agents, did not markedly influence the frequency of SCEs induced by these agents. These observations indicate that (1) the mechanisms involved in the production of ChA's and SCEs are at least partly different, (2) there is no direct relationship between SCE and PRR, and (3) caffeine must be capable of enhancing the frequency of induced ChA's not only by mechanisms connected with its inhibition of the gap-filling step of PRR, but also by other mechanisms.

204 Sugimura, T., National Cancer Center Research Institute, Tokyo (Japan) Review of submammalian systems for detecting mutagens and carcinogens