GENETIC EFFECT OF 3-CARBETHOXYPSORALEN, ANGELICIN, PSORALEN AND 8-METHOXYPSORALEN PLUS 365-NM IRRADIATION IN SACCHAROMYCES-CEREVISIAE - INDUCTION OF REVERSIONS, MITOTIC CROSSING-OVER, GENE CONVERSION AND CYTOPLASMIC PETITE MUTATIONS

The genetic effects of 2 mono-functional photosensitizing furocoumarins, 3-carbethoxypsoralen (3-CPs) and angelicin, were compared with those of 2 bi-functional furocoumarins, 8-methoxypsoralen and psoralen in S. cerevisiae. A drug concentration of 5 .times. 10-5 M plus various doses of 365 nm irradiation at a dose rate of 1.2 kJ/m-2 per min were used. Per dose of 365 nm irradiation, the frequency of induced nuclear events such as gene mutation and mitotic recombination (conversion and crossing-over) is higher for the bi-functional than for the mono-functional compounds. The higher efficiency of the bi-functional furocoumarins is also evident when the frequency of mutants is expressed as a function of survival. The photoaddition of the 4 furocoumarins studied leads to the same response for the induction of recombinational events per viable cell. Among genetically altered colonies induced in the diploid strains D5 and D7, the colonies corresponding to the induction of crossing-over are effectively produced by bi-functional furocoumarins, but are rare (D7) or even absent (D5) after treatment with monofunctional furocoumarins. This suggests a certain specificity of genetic alterations produced by the bi-functional agents. 3-CPs may be the most effective inducer on the cytoplasmic petite mutation in stationary phase cells per unit irradiation dose or per viable cell. [The drugs tested are of use in psoriasis therapy; human applicability is implied].