Deficient G2 phase repair of radiation-induced chromatin damage in the SENCAR mouse.
The SENCAR mouse, selectively bred for sensitivity to skin tumor induction by two-stage chemical carcinogenesis, is also genetically hypersensitive to skin carcinogenesis by high doses of UV. Skin fibroblasts from the SENCAR mouse exposed during G2 phase to radiation associated with intracellular hydroxyl radical formation, i.e. X-rays or near UV/visible light, showed a higher frequency of chromatid breaks at 2 h post-irradiation than skin fibroblasts from six other inbred strains of mice including C3H/HeN. However the level was similar to that reported previously for the BALB/cAn mouse known to be resistant to chemical carcinogenesis of skin. When exposed for 2 h to visible light (8 W/m2), chromatid breaks persisted in fibroblasts from the SENCAR mouse during the 4 h post-irradiation period, but showed an abrupt decline in C3H/HeN fibroblasts within 1 h after irradiation. Skin fibroblasts from the tumor-sensitive SENCAR mouse differed from those of the resistant BALB/cAn in response to beta-cytosine arabinoside (ara-C) an inhibitor of the repair polymerase. Ara-C added to cultures of SENCAR and BALB/cAn cells after G2 X-irradiation (68R) increased chromatid gaps 18-fold and breaks 2-fold in BALB/cAn cells but had no effect on SENCAR cells even though incorporated into DNA to the same extent. The present results suggest that the SENCAR mouse is deficient in at least two aspects of DNA repair: (i) ligation or a prior step in the repair process leading to ligation and (ii) repair endonucleolytic incision at DNA lesions induced by irradiation.
Sanford
K K
KK
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Parshad
R
R
Price
F M
FM
Gantt
R
R
Jones
G M
GM
Tarone
R E
RE
D000818:Animals; D002478:Cells, Cultured; D002842:Chromatids / Q000528:radiation effects; D002843:Chromatin / Q000528:radiation effects*; D004260:DNA Repair; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D007399:Interphase / Q000528:radiation effects*; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D012867:Skin / Q000166:cytology / Q000528:radiation effects*; D013045:Species Specificity; D014466:Ultraviolet Rays; D014965:X-Rays
D002843:Chromatin