Induction of DNA-DNA Cross-Link Formation in Human Cells by Various Psoralen Derivatives1
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چکیده
Furocoumarin-induced DNA damage, monoadducts, and cross-links were measured in normal human, xeroderma pigmentosum, and Panconi's anemia cells after exposure to near-UV (356 nm). At similar concentrations and near-UV doses, photoad dition by 8-methoxypsoralen was twice that by angelicin and the substitution of bromodeoxyuridine for thymidine in one strand of DNA did not alter the binding. The rate of cross-linking by 8methoxypsoralen was twice that of 5-methoxypsoralen. Low frequencies of cross-links were detected from angelicin and 3carbethoxypsoralen but none were detected from 5-geranoxypsoralen at concentrations up to 25 /¿g/mland near-UV doses up to 45,000 J/m2.
منابع مشابه
Induction of DNA-DNA cross-link formation in human cells by various psoralen derivatives.
Furocoumarin-induced DNA damage, monoadducts, and cross-links were measured in normal human, xeroderma pigmentosum, and Fanconi's anemia cells after exposure to near-UV (356 nm). At similar concentrations and near-UV doses, photoaddition by 8-methoxypsoralen was twice that by angelicin and the substitution of bromodeoxyuridine for thymidine in one strand of DNA did not alter the binding. The ra...
متن کاملFormation and repair of psoralen-DNA adducts and pyrimidine dimers in human DNA and chromatin.
DNA damage and repair in human cells exposed to ultraviolet light (254 nm) or to psoralen derivatives plus 360 nm light were compared by means of a variety of analytic techniques. The two kinds of damage show considerable structural similarity; both involve cyclobutyl bonds to 5,6 positions of pyrimidines as major products and have various minor products. In purified DNA, pyrimidine dimers, but...
متن کاملRepair of interstrand cross-links in DNA induced by psoralen plus light.
The clinical drug psoralen, in the presence of 360-nm light, binds to cellular DNA, forming monofunctional adducts with pyrimidine bases and interstrand cross-links. Cross-links, however, rather than monoadducts, appear to be the DNA lesion primarily responsible for the sensitizing action of this drug. Formation of an interstrand cross-link necessarily damages both DNA strands at nearly the sam...
متن کاملMismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells.
DNA interstrand crosslinks (ICLs) present formidable blocks to DNA metabolic processes and must be repaired for cell survival. ICLs are induced in DNA by intercalating compounds such as the widely used therapeutic agent psoralen. In bacteria, both nucleotide excision repair (NER) and homologous recombination are required for the repair of ICLs. The processing of ICLs in mammalian cells is not c...
متن کاملPsoralen-induced DNA interstrand cross-links block transcription and induce p53 in an ataxia-telangiectasia and rad3-related-dependent manner.
Psoralen plus UVA light (PUVA) is commonly used to treat psoriasis, a common skin disorder associated with rapid proliferation of cells. PUVA exerts its antiproliferative activity through formation of DNA monoadducts and interstrand cross-links (ICLs). However, this treatment may lead to skin malignancies as a direct result of inducing carcinogenic DNA damage. Inactivation of the p53 tumor supp...
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تاریخ انتشار 2006