title: Radiation-induced chromatid aberrations in Cockayne syndrome and xeroderma pigmentosum group C fibroblasts in relation to cancer predisposition.
abstract: We showed previously that the persistence of chromatid breaks and gaps after G2 phase irradiation with X-rays or near-UV visible light characterizes skin fibroblasts from individuals with cancer-prone genetic diseases. This abnormal response appears to result from deficient DNA repair during G2 and to be associated with cancer proneness. We have, therefore, compared the responses of cells from two genetic disorders, Cockayne syndrome (CS) and xeroderma pigmentosum complementation group C(XP-C), both of which exhibit cellular hypersensitivity to sunlight, but only one of which, XP, manifests a high rate of sunlight-induced cancer. CS cells, in contrast to XP cells, showed a normal G2 response to irradiation with either X-rays or near-UV visible light. However, CS cells showed a deficiency in repair of DNA damage inflicted by light during S and G1 phases of the cell cycle. The present results support the concept that deficient DNA repair during G2 phase plays a role in carcinogenesis. This deficient repair in the presence of DNA damage and continuous cell cycling from activation of proto-oncogenes or loss of suppressor genes may be necessary and sufficient for cancer development.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: F M
authors.initials: FM
authors.lastname: Price
authors.forename: R
authors.initials: R
authors.lastname: Parshad
authors.forename: R E
authors.initials: RE
authors.lastname: Tarone
authors.forename: K K
authors.initials: KK
authors.lastname: Sanford
mesh_terms: D015984:Causality; D002478:Cells, Cultured; D002842:Chromatids / Q000528:radiation effects; D002869:Chromosome Aberrations; D003057:Cockayne Syndrome / Q000235:genetics*; D003561:Cytarabine / Q000494:pharmacology; D004260:DNA Repair; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000235:genetics; D014965:X-Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D003561:Cytarabine