Role of postreplication repair in transformation of human fibroblasts to anchorage independence
- Univ. of North Carolina, Chapel Hill (USA)
Cellular capacity for postreplication repair (PRR) and sensitivity to transformation to anchorage independence (AI) were quantified in normal foreskin and 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 of DNA damaged by genotoxic agents. It is recognized biochemically as the process by which nascent DNA grows longer than the average distance between two lesions in the DNA template. PRR refers more directly to the elimination of gaps in the daughter-strand DNA by mechanisms which remain to be determined for human cells, but which may include translesion replication and recombination. PRR was measured in diploid human fibroblasts by analysis of the dose kinetics for inhibition of DNA strand growth in carcinogen-treated cells. Logarithmically growing foreskin fibroblasts (NHF1) displayed D0 values of 4.3 J/m{sup 2} and 0.14 microM for the inhibition of DNA synthesis in active replicons by UV and BPDE-I, respectively. XP variant cells (CRL1162) exhibited corresponding D0 values of 1.5 J/m{sup 2} and 0.16 microM. The increased sensitivity to inhibition of DNA replication by UV in these XP variant fibroblasts (2.9-fold greater than normal) was mirrored by an enhanced frequency of transformation to AI. XP variant fibroblasts (CRL1162) were 3.2 times more sensitive to transformation to AI by UV than were the normal foreskin fibroblasts. As predicted by the PRR studies, both cell types exhibited similar frequencies of AI colonies induced by BPDE-I. Apparent thresholds were observed for induction of AI by UV (normal fibroblasts, 2.7 J/m{sup 2}; XP variant fibroblasts, 0.3 J/m{sup 2}) and BPDE-I (both, 0.05 microM).
- OSTI ID:
- 5553796
- Journal Information:
- Cancer Research; (United States), Vol. 51:11; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
EPOXIDES
GENETIC EFFECTS
XP CELLS
DNA REPAIR
CARCINOGENS
DNA REPLICATION
FIBROBLASTS
MAN
ULTRAVIOLET RADIATION
XERODERMA PIGMENTOSUM
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONNECTIVE TISSUE CELLS
DISEASES
ELECTROMAGNETIC RADIATION
MAMMALS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PRIMATES
RADIATIONS
RECOVERY
REPAIR
SKIN DISEASES
SOMATIC CELLS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 - Chemicals Metabolism & Toxicology