Lethal and mutagenic effects photoinduced in haploid yeast (Saccharomyces cerevisiae) by two new monofunctional pyridopsoralens compared to 3-carbethoxypsoralen and 8-methoxypsoralen.
The photobiological effects of two monofunctional pyridopsoralens (PPs), pyrido[3,4-c]psoralen and pyrido[3,4-c]-7-methylpsoralen were studied and compared to those of 3-carbethoxypsoralen (3-CPs) and 8-methoxypsoralen (8-MOP) in a haploid wild-type strain of yeast (Saccharomyces cerevisiae). The capacity of PPs to photoinduce lethal effects in the presence of 365-nm radiation was not only higher than that of the monofunctional compound 3-CPs, but also higher than that of the bifunctional compound 8-MOP. This activity was apparently independent of oxygen, and it was found that it was probably due to the induction of monoadducts in DNA. A high effectiveness of PPs on the induction of cytoplasmic 'petite' mutations was observed suggesting a high photoaffinity towards mitochondrial DNA. In contrast to 8-MOP, the strong cell killing activity of PPs was not accompanied by a strong inducing effect on nuclear mutations (HIS+ reversions or canR forward mutations). For these endpoints, PPs were less effective per unit dose of 365-nm radiation and also less efficient per viable cell than 8-MOP. From this, it appears that the lesions photoinduced by the former compounds show a more lethal than (nuclear) mutagenic potential. Furthermore, the fact that PPs were even less mutagenic (nuclear) per viable cell than the monofunctional compound 3-CPs suggests that the activity of these agents may differ in frequency and nature of lesions induced. The photobiological activity of PPs in haploid yeast appears to be in line with the recent proposition for their use in photochemotherapy.
D004271:DNA, Fungal / Q000235:genetics; D011564:Furocoumarins / Q000633:toxicity*; D006238:Haploidy; D008730:Methoxsalen / Q000633:toxicity; D009154:Mutation / Q000187:drug effects; D010777:Photochemistry; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D004271:DNA, Fungal; D011564:Furocoumarins; C044263:pyrido(3,4-c)psoralen; C044264:pyrido(3,4-c)-7-methylpsoralen; C017104:3-carbethoxypsoralen; D008730:Methoxsalen