DNA photobinding of 7-methylpyrido[3,4-c]psoralen and 8-methoxypsoralen. Effects on macromolecular synthesis, repair and survival in cultured human cells |
| |
Authors: | S Nocentini |
| |
Affiliation: | 1. Plant Bioactives Group, Post-Harvest and Agro-Processing Technologies, Agricultural Research Council (ARC) Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa;2. Department of Food Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa;3. Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa;1. Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China;2. Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, China;3. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, China |
| |
Abstract: | The photobinding to DNA of tritiated 7-methylpyrido[3,4-c]psoralen (MPP), a recently synthesized monofunctional compound of therapeutical interest, and of 8-methoxypsoralen (8-MOP) was determined in cultured normal human fibroblasts. Employing compounds at 10(-6) M, MPP photobinds approximately 11 times more efficiently than 8-MOP: one molecule is fixed respectively per 7.5 X 10(4) or 8.1 X 10(5) base pairs/kJ . m-2 of 365-nm radiation (UVA). Removal of bound material from DNA is slow and limited in 48-72 h of post-treatment incubation to 30-40% of initial adducts formed by MPP and to 50-60% of those of 8-MOP. For equivalent photobinding MPP and 8-MOP induce similar inhibitions of DNA synthesis. However, the recovery of DNA synthesis during post-treatment incubation is lower after photoaddition of MPP than after that of 8-MOP. MPP also exerts a much higher lethal effect than 8-MOP: one lethal hit corresponds to about 4400 and to 19,900 adducts per cell respectively. Alkaline elution experiments confirmed the monofunctional nature of MPP and indicated that in MPP-damaged cells DNA breaks accumulate with time of post-treatment incubation. In contrast, after photoaddition of 3-carbethoxypsoralen (3-CPs), another monofunctional furocoumarin, or irradiation with 254-nm UV, DNA breaks are induced only transiently. In 8-MOP-treated cells, DNA cross-links appear to be partially repaired. In conclusion, MPP monoadducts turn out to constitute more cytotoxic lesions than 8-MOP mono- and bi-adducts. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|