METABOLISM OF 7,12-DIMETHYLBENZ(A)ANTHRACENE BY MACROPHAGES AND UPTAKE OF MACROPHAGE-DERIVED METABOLITES BY RESPIRATORY TISSUES INVITRO

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (4) , 1079-1084
Abstract
Cultured mouse macrophages and tracheal and lung tissue each produced the same ethyl acetate-soluble derivatives of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The derivatives produced in the different cultures were indistinguishable by TLC and high-pressure liquid chromatography but differed in their relative proportions. The greatest difference was seen between lungs and macrophages. The predominant metabolite produced by lungs was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene, while macrophages produced equal quantities of 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene and a 2nd uncharacterized derivative, metabolite B, at low DMBA doses (< 0.05 .mu.g/ml medium) and primarily metabolite B at higher DMBA doses (> 0.05 .mu.g/ml medium). Macrophages released the majority of the ethyl acetate-soluble metabolites produced into the surrounding medium. With the exception of 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene, these derivatives were accumulated within tracheal and lung tissue when these organs were cocultivated with macrophages in the presence of DMBA.