Enhancement of base pair substitution induced by alkylating mutagens in simulated hyperbaric diving environments

The effect of simulated saturated diving environments on mutagenicity was investigated using two histidine auxotrophs (hisG46 and hisTA1950 derived by Ames from Salmonella typhimurium LT2) exposed to several chemical mutagens. In agar diffusion tests with impregnated paper discs, 68 atm of normoxic supporting gases (containing 0.2 atm O2) reduced the number of histidine revertants of auxotrophs exposed to N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and two other alkylating agents. The effect was induced in increasing order by helium, a mixture of neon and helium, nitrogen and argon. The effect of the gases on the growth of the two strains was small and did not explain the reduction of revertant recovery. On the other hand, it was shown that NTG in concentrations of 0.6 to 250 mug/ml was significantly more lethal for the hisG46 strain under 68 and 136 atm than at 1 atm. Revertant recovery was similarly related in both conditions. The maximal number of revertants, approx. 2.6 X 10(4), was obtained at 136 atm when the concentration of NTG was 0.6--1.25 mug/ml and at 1 atm when the concentration of NTG was 5--10 mug/ml. A comparable hydrostatic environment did not affect revertant recovery. The most plausible interpretation of these results is that hyperbaric environments accelerate the rate of intracellular accumulation of NTG, which is manifest in greater mutagenicity at the lower concentrations and greater lethality at all concentrations.