Evidence of DNA repair/processing defects in cultured skin fibroblasts from breast cancer patients

Citation
Ma. Hannan et al., Evidence of DNA repair/processing defects in cultured skin fibroblasts from breast cancer patients, CANCER RES, 61(9), 2001, pp. 3627-3631
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
61
Issue
9
Year of publication
2001
Pages
3627 - 3631
Database
ISI
SICI code
0008-5472(20010501)61:9<3627:EODRDI>2.0.ZU;2-Y
Abstract
Cultured skin fibroblasts from 14 breast cancer (BC) patients were compared with those from 8 healthy subjects and 4 ataxia-telangiectasia (A-T) cases for sensitivity to low dose-rate (0.007 Gy/min) gamma -irradiation assesse d by a colony-forming assay and for postirradiation DNA synthesis inhibitio n determined by the method of [H-3]thymidine incorporation. Fibroblasts fro m all but two DC patients exhibited moderately enhanced radiosensitivity in the colony-forming assay, occupying an intermediate position between the c ontrols and the A-T cases. Fibroblasts from the radiosensitive BC patients also showed an intermediate response with respect to radio-induced DNA synt hesis inhibition compared with those from controls and A-T cases. In a host cell reactivation assay using an irradiated herpes simplex virus Fur plaqu e-forming: ability, the fibroblasts from 7 BC patients, used as host cells, resulted in a significantly reduced (P < 0.0001) recovery of the virus rel ative to the 8 control Fibroblasts, suggesting a deficiency in DNA repair i n the Former. A number of the BC fibroblasts analyzed in an assay for poten tially lethal damage repair confirmed the repair deficiency in the fibrobla sts from the BC patients. Defects in DNA repair and/or DNA processing after exposure to genotoxic agents would lead to genomic instability and hence w ould be responsible for cancer predisposition, Our data suggest that most D C patients may carry various genes resulting in such defects, and additiona l studies on normal cells from a larger cohort of DC patients and their fam ily members are warranted to establish a connection between mutations or po lymorphisms in specific DNA repair genes and susceptibility to breast cance r.