It has been shown previously that an in vitro system involving N- hydroxyacetyl-aminofluorene (N-OH-AAF), the intermediate activated form of an arylamine carcinogen, can be activated by peroxidase enzymes, via free-radical events, to form two more potent carcinogens. We present preliminary data here that help to understand this potentially very important activation system and which question the validity of the original scheme. We propose experiments which will determine the nature of the carcinogen free radicals produced in this reaction, and the reactivity of these intermediates with important cellular constituents. We also propose experiments to determine if female rat mammary gland tissues susceptible to these carcinogens yet void of other known activation mechanism contain enzymes capable of carrying out the peroxidative type activation mechanism. We also present preliminary data of a reaction we have discovered which involves organic peroxides and heme compounds (including microsomes and catalase, among others), and converts N-OH-AAF stoichiometrically into products the nature of which are not known. We have preliminary data that indicate carcinogen free radicals are intermediates in this general reaction. We bedieve this reaction to be of considerable importance because in preliminary work catalase utilizing cumene hydroperoxide converted N-OH-AAF into what we have inferred to be nitrosofluorene, a more potent carcinogen. We propose experiments to help clarify this reaction as to the intermediates involved, the products formed and if it will occur with naturally occurring peroxides. We propose low-temperature-ESR experiments to help clarify why different products formed are dependent upon the heme compound and peroxide used.
NIH ExPorter
NIH ExPorter