Pyrolysis products from amino acids and protein: Highest mutagenicity requires cytochrome P 1 -450

Abstract

Pyrolysis products of proteins and amino acids are highly mutagenic, but metabolism of these chemicals by rat liver subcellular fractions is required for production of the mutagenic intermediates. The mutagenesis by 7 purified pyrolysis products from Tp, Lys, Glu and soybean globulin was examined with Salmonella typhimurium strain TA98 in the presence of liver fractions from genetically responsive C57BL/6N and Ahb/Ahd or nonresponsive DBA/2N and Ah3/Ahd mice that had been pretreated in vivo with benzo[a]pyrene. For all pyrolysis products tested, mutagenesis is 2- to > 1000-fold greater with C57BL/6N and Ahb/Ahd than with DBA/2N or Ah3/Ahd liver fractions. A sucrose density gradient assay for detecting the Ah regulatory gene product, the receptor, was studied with C57BL/6N hepatic cytosol. At levels 100 times in excess of [1,6-3H]2,3,7,8-tetrachlorodibenzo-p-dioxin, nonlabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene and .beta.-naphthoflavone (inducers of cytochrome P1-450) are able to displace the radiological from its hepatic cytosolic receptor; 4 pyrolysates from Trp, Glu and soybean globulin did not have this capacity. The pyrolysis products tested, although not effective as inducers of cytochrome P1-450, are most mutagenic when metabolized by P1-450. Potent P1-450 inducers-present in pyrolysates during the combustion process-might be present in quantities insufficient to initiate mutagenesis or carcinogenesis but might have a synergistic action, or act as comutagens or cocarcinogens, with the N-containing heterocyclic pyrolysis products. A quantitative relationship between mutagenic and carcinogenic potency of these pyrolysis products remains to be demonstrated.