Photochemotherapy using pyridopsoralens.
Aiming to decrease the acute side effects and genotoxic hazards of PUVA, pyrido (3,4-C) psoralen (PP) and 7-methyl pyrido (3,4-C) psoralen (MPP) were synthesized and studied. Their UVA maximum absorption lies at 325 and 330 nm, respectively. Their photostability is comparable to that of 8-MOP. They complex to DNA in the dark, and, in the presence of UVA, produce only monoadditions to DNA, as shown by fluorescence and DNA denaturation-renaturation studies. In diploid eukaryotic yeast they are more effective than 8-MOP for the induction of lethal effects and mitochondrial damage. Their mutagenic activity per unit dose of UVA is in the same range as that of 8-MOP. However, per viable cell they are clearly less mutagenic than 8-MOP. This difference is also observed for recombinogenic activity. No oxygen effect is observed. In mammalian cells the following ranges of effectiveness are found: inhibition of DNA synthesis in human fibroblasts: MPP greater than PP greater than 8-MOP; mutagenic activity in V79 Chinese hamster cells: MPP greater than PP greater than 8-MOP; cell transforming ability in C3H embryonic mouse cells: MPP greater than 8-MOP greater than PP as a function of UVA dose, and: 8-MOP greater than MPP greater than PP as a function of survival; induction of sister chromatic exchanges (SCE) per unit dose: MPP greater than PP greater than 8-MOP in the linear part of the induction curve, and : 8-MOP greater than PP greater than MPP at the maximum level of SCE obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
D000078223:5-Methoxypsoralen; D000818:Animals; D002280:Basal Cell Carcinoma / Q000139:chemically induced; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced; D011564:Furocoumarins / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008730:Methoxsalen / Q000009:adverse effects / Q000627:therapeutic use; D009152:Mutagenicity Tests; D009154:Mutation; D011701:PUVA Therapy / Q000009:adverse effects / Q000379:methods; D010146:Pain; D010777:Photochemistry; D010859:Pigmentation Disorders / Q000139:chemically induced; D012878:Skin Neoplasms / Q000139:chemically induced
D011564:Furocoumarins; D000078223:5-Methoxypsoralen; C044263:pyrido(3,4-c)psoralen; C044264:pyrido(3,4-c)-7-methylpsoralen; C017104:3-carbethoxypsoralen; D008730:Methoxsalen