EFFECT OF SALMONELLA ASSAY NEGATIVE AND POSITIVE CARCINOGENS ON INTRACHROMOSOMAL RECOMBINATION IN S-PHASE ARRESTED YEAST-CELLS

A wide variety of carcinogens including Ames assay (Salmonella) positi ve as well as Salmonella negative carcinogens induce intrachromosomal recombination (DEL recombination) in Saccharomyces cerevisiae. We have shown previously that the Salmonella positive carcinogens, ethyl meth anesulfonate (EMS), methyl methanesulfonate (MMS) and 4-Nitroquinoline -N-oxide (4-NQO, and the Salmonella negative carcinogens, safrole, ben zene, thiourea, carbon tetrachloride, and urethane, induced DEL recomb ination in growing, in G1 and in G2 arrested yeast cells. Since we fou nd interesting differences in response between dividing and arrested c ells, we wanted to find out whether these differences were due to the difference between cell division versus cell cycle arrest or to any pa rticular cell cycle phase. In the present paper we incubated cells in the presence of hydroxyurea (HU) for cell cycle arrest in S-phase and exposed them to the above carcinogens, and plated them onto selective medium to determine DEL and interchromosomal recombination (ICR) frequ encies. It was surprising that carbon tetrachloride had no effect on D EL recombination or ICR in HU treated cells even though it induced DEL recombination in G1 and G2 arrested as well as dividing cells. Furthe r experiments are in agreement with the interpretation that carbon tet rachloride was responsible for prematurely pushing G1 cells into S-pha se. The consequence of this may be replication on a damaged template w hich may be responsible for the action of carbon tetrachloride. EMS, M MS, 4-NQO and urethane were more recombinagenic in HU treated cells th an in previous experiments with G2 arrested cells. None of the carcino gens appeared to be activated by S9 for either DEL recombination or IC R induction. Furthermore, we only detect cytochrome P-450 in dividing but not in arrested cells, arguing that possible differences in the ab ility to metabolize the compounds does not explain the observed differ ences for DEL recombination induction in the different cell cycle phas es, We discuss these data in terms of the mechanism of induced DEL rec ombination and the possible biological activities of these carcinogens . (C) 1998 Elsevier Science B.V. All rights reserved.