Pyrolysis products from amino acids and protein: Highest mutagenicity requires cytochrome P1-450

AUTOR(ES)

Nebert, Daniel W.

RESUMO

Pyrolysis products of proteins and amino acids are highly mutagenic, but metabolism of these chemicals by rat liver subcellular fractions is known to be required for production of the mutagenic intermediates. We examined the mutagenesis of seven purified pyrolysis products from tryptophan, lysine, glutamic acid, and soybean globulin with Salmonella typhimurium strain TA98 in the presence of liver fractions from genetically “responsive” C57BL/6N and Ahb/Ahd or “nonresponsive” DBA/2N and Ahd/Ahd mice that had been pretreated in vivo with benzo[a]pyrene. For all pyrolysis products tested, mutagenesis is 2-fold to more than 1000-fold greater with C57BL/6N and Ahb/Ahd than with DBA/2N or Ahd/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 β-naphthoflavone (inducers of cytochrome P1-450) are able to displace the radioligand from its hepatic cytosolic receptor; four pyrolysates from tryptophan, glutamic acid, and soybean globulin did not have this capacity.

Documentos Relacionados

• Localization of cytochrome P1-450 and P3-450 genes to mouse chromosome 9.
• Transfection by genomic DNA of cytochrome P1-450 enzymatic activity and inducibility.
• In situ protein-DNA interactions at a dioxin-responsive enhancer associated with the cytochrome P1-450 gene.
• Control of cytochrome P1-450 gene expression: analysis of a dioxin-responsive enhancer system.
• Assignment of the human 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome P1-450 gene to chromosome 15.