0000000000937546
AUTHOR
Thomas M. Rünger
Is the repair of oxidative DNA base modifications inducible by a preceding DNA damage induction?
In mammalian cells, 7,8-dihydro-8-oxoguanine (8-oxoG) and some other oxidative guanine modifications are removed from the DNA by base excision repair, which is initiated by OGG1 protein. We have tested whether this repair is inducible in mouse embryonic fibroblasts (MEFs), MCF-7 breast cancer cells and primary human fibroblasts by a pretreatment with the photosensitizer Ro19-8022 plus light, which generates predominantly 8-oxoG, or with methyl methanesulfonate (MMS), which generates alkylated bases and abasic sites (AP sites). The results indicate that the repair rate of the oxidative guanine modifications induced by the photosensitizer was not increased if a priming dose of the oxidative o…
Alterations of DNA Repair in Melanoma Cell Lines Resistant to Cisplatin, Fotemustine, or Etoposide
Resistance to chemotherapy is a common phenomenon in malignant melanoma. In order to assess the role of altered DNA repair in chemoresistant melanoma, we investigated different DNA repair pathways in one parental human melanoma line (MeWo) and in sublines of MeWo selected in vitro for drug resistance against four commonly used drugs (cisplatin, fotemustine, etoposide, and vindesine). Host cell reactivation assays with the plasmid pRSVcat were used to assess processing of different DNA lesions. With ultraviolet-irradiated plasmids, no significant differences were found, indicating a normal (nucleotide excision) repair of DNA photoproducts. With singlet oxygen-treated plasmid, the fotemustine…
Modulation of Base Excision Repair Alters Cellular Sensitivity to UVA1 but not to UVB¶
Abstract Oxidative DNA damage has been implicated in some of the biological properties of UVA but so far not in the acute photosensitivity or cellular sensitivity. In contrast to pyrimidine dimers, oxidative DNA damage is predominantly processed by base excision repair (BER). In order to further clarify the role of oxidative DNA damage and its repair in the acute cellular response to UV light, we studied UVA1 and UVB sensitivities in three different cell model systems with modified BER. 8-Oxoguanine-DNA-glycosylase 1–/– (OGG1–/–) mouse embryonal fibroblasts and human fibroblasts in which BER was inhibited by incubation with methoxyamine were hypersensitive to UVA1, in particular to low dose…