Mutagenicity testing of antischistosomal thioxanthenones and indazoles on yeast

Two antischistosomal thioxanthenones, lucanthone and hycanthone, and four antischistosomal indazoles, IA-3, IA-4, IA-5, and IA-6, have been tested for mutagenicity on stationary phase cells of the yeast Saccharomyces cerevisiae. It was shown that, although there are some gaps in the data, hycanthone and IA-6 are mutagenic at pH 7.0, hycanthone is mutagenic at 5.9, and none of the other compounds is mutagenic at either pH. (Because mutagenicity of these compounds at pH 7.0 appears to be related to the presence of a methoxy group at position 5 of the polycyclic ring, it is possible that IA-4 will be mutagenic on yeast when it is tested at pH 7.0.) An excision-repair-deficient strain of yeast is no more sensitive than other strains. It was found from time-concentration studies on lethality that an inverse relation held: cells exposed to a mutagenic compound are more sensitive when time of exposure was varied and concentration of the compound was held constant, and cells exposed to a nonmutagenic compound are more sensitive when concentration is varied and time of exposure held constant. When the compounds were tested on growing cells of yeast in rich media, none of the compounds is mutagenic, although some are lethal. The kinetic behavior in reversion of yeast exposed to these compounds shows marked departures from similar reversion studies where yeast is exposed to radiation, implicating different physiological mechanisms for the alteration of responses of yeast cells exposed to the different mutagens.