These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Comparison of acyltransferase-mediated mutagenicity and nucleic acid binding of N-acetoxy-4-acetylaminobiphenyl by hepatic and bladder microsomes from rats and dogs.
    Author: Swaminathan S, Hatcher JF.
    Journal: Environ Mol Mutagen; 1992; 20(1):61-72. PubMed ID: 1379179.
    Abstract:
    Acyltransferase-mediated mutagenic and metabolic activation of N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP) by hepatic tissues of rats and dogs were compared. N-OAc-AABP was mutagenic in Salmonella typhimurium TA98 even in the absence of exogenous enzyme(s). However, supplementation with hepatic microsomes from dogs showed a dose-dependent increase in mutagenicity of N-OAc-AABP, whereas under the same conditions, rat microsomes were inactive. Incubation of liver microsomes with RNA showed that 46.4 and 11.2 nmole of [3H]N-OAc-AABP were bound/mg RNA/mg protein with dogs and rats, respectively. The hepatic microsome-mediated binding and mutagenicities of N-OAc-AABP were blocked by paraoxon, suggesting the involvement of deacetylase(s) in the activation process. Analyses of the in vitro incubates of N-OAc-AABP with rat and dog liver microsomes revealed the O-deacetylation product N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) as the major metabolite. The ratios of O-deacetylation of N-O[14C]Ac-AABP versus N-deacetylation of N-OAc-[14C]AABP for hepatic microsomes from dogs and rats were 2.9 and 7.2, respectively. The O- and N-deacetylases are also distributed in bladder tissues and their activities in comparison to the hepatic tissues were lower and amounted to 14.2 and 5.0 nmoles (O/N-deacetylation ratio 2.8) for dogs and 14.8 and 1.7 nmoles per mg protein per min (O/N-ratio of 8.7) for rats. The microsomes from bladder tissues also catalyzed the binding of [3H]N-OAc-AABP to RNA and enhanced its mutagenic response in TA98, both of which were blocked by paraoxon. The occurrence of deacetylase(s) in the target tissues of the bladder carcinogen 4-acetylaminobiphenyl (AABP) suggests that metabolic activation of some of the proximate metabolites could occur within these target organs. Furthermore, since the O-deacetylation product N-OH-AABP is relatively innocuous compared to the N-deacetylation product N-acetoxy-4-aminobiphenyl, these results imply that the refractiveness of rats for 4-aminobiphenyl or AABP-induced bladder carcinogenesis might in part be associated with the higher ratios of microsomal O/N-deacetylase activities. Thus susceptibility to arylamine or arylacetamide-induced liver and bladder carcinogenesis might be influenced by the microsomal deacetylases.
    [Abstract] [Full Text] [Related] [New Search]