Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents

Journal Article · Fri Jan 01 04:00:00 UTC 1982 · Cancer Res.; (United States)

OSTI ID:5448870

Jaspers, N G; de Wit, J; Regulski, M R; Bootsma, D

The effect of different carcinogenic agents on the rate of semiconservative DNA replication in normal and ataxia telangiectasis (AT) cells was investigated. The rate of DNA synthesis in all AT cell strains tested was depressed to a significantly lesser extent than in normal cells after exposure to X-rays under oxia or hypoxia or to bleomycin, agents to which AT cells are hypersensitive. In contrast, inhibition of DNA replication in normal human and AT cells was similar after treatment with some DNA-methylating agents or mitomycin C. Colony-forming ability of AT cells treated with these agents was not different from normal cells. Treatment with 4-nitroquinoline 1-oxide elicited a variable response in both AT and normal cell strains. In some strains, including those shown to be hypersensitive to the drug by other workers, the inhibition of DNA synthesis was more pronounced than in other cell strains, but no significant difference between AT and normal cells could be detected. The rejoining of DNA strand breaks induced by X-rays, measured by DNA elution techniques, occurred within l2 hr after treatment and could not be correlated with the difference in DNA synthesis inhibition in AT and normal cells. After low doses of X-rays, AT cells rejoined single-strand breaks slightly more slowly than did normal cells. The rate of DNA replication in X-irradiation AT and normal cells was not affected by nicotinamide, an inhibitor of poly(adenosine diphosphate ribose) synthesis. These data indicate that the diminished inhibition of DNA replication in carcinogen-treated AT cells (a) is a general characteristic of all AT cell strains, (b) correlates with AT cellular hypersensitivity, (c) is not directly caused by the bulk of the DNA strand breaks produced by carcinogenic agents, and (d) is not based on differences in the induction of poly(adenosine diphosphate ribose) synthesis between X-irradiated AT and normal cells.

• Research Organization: Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands
• OSTI ID: 5448870
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 42:1; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

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550900 -- Pathology
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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
ANOXIA
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLEOMYCIN
CELL CULTURES
DISEASES
DNA
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
IONIZING RADIATIONS
NICOTINAMIDE
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOLOGY
PYRIDINES
QUINOLINES
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
SKIN DISEASES
STRAND BREAKS
TELANGIECTASIS
VASCULAR DISEASES
VITAMIN B GROUP
VITAMINS
X RADIATION