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National Institute of Environmental Health Sciences

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Publication Detail

Title: Mutagenesis by 8-methoxypsoralen and 5-methylangelicin photoadducts in mouse fibroblasts: mutations at cross-linkable sites induced by offoadducts as well as cross-links.

Authors: Gunther, E J; Yeasky, T M; Gasparro, F P; Glazer, P M

Published In Cancer Res, (1995 Mar 15)

Abstract: Psoralens are used clinically in the treatment of several skin diseases, including psoriasis, vitiligo, and cutaneous T cell lymphoma. However, psoralen treatment has been associated with an increased risk of squamous cell carcinoma of the skin. To elucidate molecular events that may play a role in the psoralen-related carcinogenesis, we examined psoralen-induced mutagenesis in a mouse fibroblast cell line carrying a recoverable, chromosomally integrated lambda phage shuttle vector. Using the supF gene as a mutation reporter gene, we determined the spectrum of mutations induced by photoactivation of 8-methoxypsoralen and of 5-methylangelicin. Both psoralens generated predominately T:A to A:T and some T:A to G:C transversions. Most of the mutations occurred at either 5' TpA or 5' ApT sites, both of which are conducive to interstrand cross-link formation. However, 5-methylangelicin produces only monoadducts, whereas 8-methoxypsoralen generated 20% cross-links and 80% monoadducts under the conditions of our experiments, as measured by direct HPLC analysis of the DNA from the treated cells. Although most of the mutations occurred at potentially cross-linkable sites, these results implicate monoadducts, as well as cross-links, as critical premutagenic lesions in psoralen-treated mammalian cells. These findings may help in the identification of carcinogenic changes induced by psoralen, and they may aid in the improved design of psoralen-based treatment regimens in the future.

PubMed ID: 7882323 Exiting the NIEHS site

MeSH Terms: Animals; Base Sequence; Fibroblasts; Methoxsalen/toxicity*; Mice; Molecular Sequence Data; Mutagens/toxicity*; PUVA Therapy/adverse effects*; Photochemistry; Psoralens/toxicity*; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

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Last Reviewed: December 05, 2024