Role of Postreplication Repair in Transformation of Human Fibroblasts to Anchorage Independence

摘要: Cellular capacity for postreplication repair (PRR) and sensitivity to transformation anchorage independence (AI) were quantified in normal foreskin xeroderma pigmentosum (XP) variant fibroblasts after treatment with UV or benzo(a)pyrene-diol-epoxide I (BPDE-I). PRR is defined here as a collection of pathways that facilitate the replication DNA damaged by genotoxic agents. It recognized biochemically process which nascent grows longer than average distance between two lesions template. refers more directly elimination gaps daughter-strand mechanisms remain be determined human cells, but may include translesion recombination. was measured diploid analysis dose kinetics inhibition strand growth carcinogen-treated cells. Logarithmically growing (NHF1) displayed D0 values 4.3 J/m2 0.14 microM synthesis active replicons BPDE-I, respectively. XP cells (CRL1162) exhibited corresponding 1.5 0.16 microM. The increased these (2.9-fold greater normal) mirrored an enhanced frequency AI. 3.2 times sensitive AI fibroblasts. As predicted studies, both cell types similar frequencies colonies induced BPDE-I. Apparent thresholds observed induction (normal fibroblasts, 2.7 J/m2; 0.3 J/m2) BPDE-I (both, 0.05 microM). Doses above produced proportional increases operating anchorage-independent colonies. At doses same degree growth, number capable did