Early steps in mutagenesis by hycanthone.

Hycanthone, the most potent mutagen in a series of nine thiaxanthenones, is a potent inducer of nuclear immunoreactivity to antinucleoside antibodies in HeLa cells. This response indicates exposure of single-stranded DNA regions. All classes of mutagens thus far tested share this property with hycanthone. Immunoreactivity to antinucleoside antibodies was also induced by brief exposure to hycanthone, 3 microgram/ml, in human fibroblasts from three normal subjects and in fibroblasts from seven patients with DNA repair deficiencies. Unlike those of many other mutagens, the metabolic effects and immunoreactivity induction of hycanthone were readily reversible. No evidence for covalent attachment of [3H]hycanthone to HeLa macromolecules could be found. Induction of DNA repair synthesis could not be detected by autoradiography after exposure of cells to hycanthone. Exposure of single-stranded DNA regions appears to be an important feature of the mechanism of action of hycanthone as a mutagen. Both hycanthone and lucanthone intercalate with DNA, but hycanthone was much less active than was lucanthone in reducing the rapid sedimentation of cell lysate DNA in alkaline sucrose gradients. Similarities and differences, therefore, have been found in the way the potent and the weak mutagen affect DNA of HeLa cells. This may provide clues to understanding the mechanism of mutagenesis by thiaxanthenones and other mutagens.