Mutagenicity of nitrosocarbaryl and other methylating nitrosamides as related to uptake in haemophilus influenzae

Differences greater than 6,000-fold in the mutagenic potency of three nitrosamides that are methylating agents [N-methyl-N-nitrosourea (MNU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-nitrosocarbaryl (NC)] could be accounted for in part by differences in their uptake into the Haemophilus influenzae cells. Uptake was roughly correlated with the octanol/water partition coefficient. The most potent mutagen, NC, was concentrated by the cells. The least potent, MNU, was essentially excluded from the bacteria. Uptake was a linear function of concentration, whereas induction of novobiocin-resistant mutations followed higher-order kinetics. The effective dose of chemical to the bacteria (number of molecules taken up) under conditions of mutagenesis could be calculated.