The oxidative metabolism of
benzo(a)pyrene and the conjugative metabolism of
1-naphthol by explant cultures of normal human colon and colonic
tumor tissue, obtained at surgery, have been studied. After 24 hr in culture, the explants were exposed to either [1-14C]-1-
naphthol (20 to 100 microM) or [3H]-
benzo(a) pyrene (1.5 microM) for a further 1.5 to 24 hr. Both normal-appearing tissue and
tumor tissue metabolized
benzo(a)pyrene to a wide variety of organic
solvent-soluble metabolites, including monohydroxybenzo(a)
pyrenes, dihydrodiols, and tetrols.
1-Naphthol was metabolized by cultured human colonic mucosa and
tumor tissue to both its
glucuronic acid and
sulfate ester conjugates. In the normal tissues, with
naphthol (20 microM),
sulfate ester conjugation predominated. However, with the
tumor tissue,
sulfate ester conjugation decreased; thus, the percentage of
glucuronic acid conjugates, expressed as a percentage of total metabolites formed, was increased significantly compared to normal tissue. The relationship, if any, of these changes to neoplastic transformation is unclear. The technique of explant culture described in this study may be of use for the study of other facets of the pathobiology of solid
tumors.