Mutagenesis induced by a number of N-nitrosamines in a liquid phase assay was enhanced 2-8 fold on going from a pH of 7.4 to 6.5, with the degree of enhancement dependent on the compound and the reaction conditions. In general, enhancement was greatest at lower concentrations of mutagen and with compounds of lower molecular weights. With dimmethylnitrosamine (DMN) part of this effect was due to an enhanced rate of metabolism at low concentrations of DMN at a pH of 6.5. However, even at higher concentrations of DMN, mutagenesis was more effective at the lower pH despite the fact that metabolism of DMN was twice as rapid at a pH of 7.4 than 6.5. Directly acting mutagens such as N-nitroso-N-methylurea and N-methyl-N' -nitro-N-nitrosoguanidine were 2-10 times more potent at pH values of between 5.5 and 7.0 than at 7.4. No enhancement in the mutagenic activities of methyl methanesulfonate, benzo(a)pyrene or 3-methyl-cholanthrene was observed on going from a pH of 7.4 to 6.5.
ASJC Scopus subject areas
- Cancer Research