Formation of DNA-damaging and mutagenic activity in the reaction systems containing nitrite and butylated hydroxyanisole, tryptophan, or cysteine.

Abstract

DNA-damaging activities were formed in the reaction systems containing nitrite and phenol derivatives including BHA [butylated hydroxyanisole], Trp or Cys under [mammalian] gastric pH conditions. The mutagenic action of the nitrite-BHA, nitrite-Trp and nitrite-Cys systems was also tested according to Ames'' method using Salmonella typhimurium TA 1535 and TA 98. The mutagenic activity was observed in the nitrite-Trp and nitrite-Cys systems, although the nitrite-BHA system did not show the activity. The DNA-damaging products were generally labile, i.e., the activity decreased significantly after 1.5-2 h of the reaction, except in the case of the nitrite-BHA system. The DNA-damaging activity in the nitrite-BHA system did not decrease even after 48 h of the reaction. Nitrosophenol derivatives themselves showed DNA-damaging activity at pH 1. The active product in the nitrite-BHA system was isolated and the structure was determined to be 2-tert-butylquinone. This compound gave a positive rec-assay test, and showed no mutagenesis by Ames'' method. The active product from the nitrite-Cys system was inferred to be nitrosocysteine, and the product showed both DNA-damaging and mutagenic activity.