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

• Published in: Journal of nutritional science and vitaminology 1979, Vol.25 (4), p.317-332
• Main Authors: Natake, M, Danno, G, Maeda, T, Kawamura, K, Kanazawa, K
• Format: Article
• Language: English
• Subjects: Anisoles - pharmacology; Butylated Hydroxyanisole - pharmacology; Cysteine - pharmacology; DNA - antagonists & inhibitors; Mutagens - isolation & purification; Nitrites - pharmacology; Recombination, Genetic; Salmonella typhimurium - drug effects; Tryptophan - pharmacology
• ISSN: 0301-4800; 1881-7742
• DOI: 10.3177/jnsv.25.317

It was confirmed by the procedure of rec-assay that DNA-damaging activities were formed in the reaction systems containing nitrite and phenol derivatives including BHA, tryptophan or cysteine under gastric pH conditions. The mutagenic action of the nitrite-BHA, nitrite-tryptophan and nitrite-cysteine systems was also tested according to Ames' method using Salmonella typhimurium TA 1535 and TA 98. The mutagenic activity was observed in the nitrite-tryptophan and nitrite-cysteine systems, though 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 to 2 hours 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 hours of the reaction. Nitrosophenol derivatives themselves showed the 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-butyl-quinone. This compound gave a positive rec-assay test, and showed no mutagenesis by Ames' method. The active product from the nitrite-cysteine system was infered to be nitrosocysteine, and the product showed both DNA-damaging and mutagenic activity.