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  • Title: Stimulation of microsomal dimethylnitrosamine-N-demethylase by pretreatment of mice with acetone.
    Author: Sipes IG, Slocumb ML, Holtzman G.
    Journal: Chem Biol Interact; 1978 Jun; 21(2-3):155-66. PubMed ID: 679394.
    Abstract:
    To further investigate the relationship between in vivo microsomal enzyme modifiers and in vitro dimethylnitrosamine (DMN) metabolism, male C57BL/6J mice were pretreated with acetone or Aroclor 1254, two compounds known to influence DMN-N-demethylase activity. Pretreatment with acetone enhanced the in vitro microsomal activity of DMN-N-demethylase, as measured by formaldehyde production from DMN. Accompanying this acetone-enhanced demethylase activity was an increase in the covalent binding of [14C]DMN to RNA, protein and DNA. Four distinct Km values dependent on the substrate concentration were observed for the N-demethylase present in control microsomes. Only one Km value was observed for the demethylase in microsomes from acetone-treated animals, but it was significantly lower than the lowest Km observed in the control microsomes. At DMN concentrations of 1 and 10 mM, acetone significantly increased N-demethylation of DMN as compared to control, but not at 100 mM DMN. Aroclor 1254 pretreatment repressed DMN-N-demethylase at 1 mM DMN but enhanced it at 100 mM. These results suggest that there may be multiple forms of DMN-N-demethylase which are dependent on DMN concentration and respond differently to modifiers of the microsomal drug-metabolizing enzymes.
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