Search PubMed⌕ Search

Biomedical subjects

D Bootsma

Publications and source records attributed to D Bootsma.

At least 109 records · Page 6Linked to original sources
PubMed1982

Abnormal levels of UV-induced unscheduled DNA synthesis in ataxia telangiectasia cells after exposure to ionizing radiation.

In cultured cells from normal individuals and from patients having ataxia telangiectasia (AT) the rate of unscheduled DNA synthesis (UDS) induced by UV light was investigated by autoradiography. The number of grains in 6 different AT cell strains was similar to that observed in normal cells. Exposure of normal cells to doses of X-rays up to 20 krad had no influence on the rate of UV-induced UDS. In contrast, the UV-induced UDS was significantly modified in AT cells by treatment with X-rays. In AT cell strains that were reported to have reduced levels of gamma-ray-induced repair DNA synthesis ('excision-deficient' AT cells) the effect of X-rays on UV-induced UDS was inhibitory, whereas UV-induced UDS was stimulated by X-ray exposure in 'excision-proficient' AT cell strains. Different UV and X-ray dose-response relationships were seen in the two categories of AT cell strains. These results strongly suggest that different molecular defects are present in excision-deficient and excision-proficient At cells. They also indicate that the altered levels of repair DNA synthesis after exposure to UV in AT cells may be a secondary consequences of the way such cells handle DNa damage caused by ionizing radiation.

Ataxia Telangiectasia↗
PubMed1982

Isolation of Chinese hamster ovary cells with reduced unscheduled DNA synthesis after UV irradiation.

A simple procedure has been worked out to obtain UV-sensitive mutants of Chinese hamster ovary (CHO) cells. In this procedure, conventional mutagenesis is followed by BrdU--light treatment to enrich the population for UV-sensitive cells. Colonies that are allowed to form subsequently are duplicated by replica plating and screened on the master plate for their UV sensitivity and their capacity to carry out UV-induced DNA repair synthesis. Putative mutants are isolated from the replica. With this combination of methods, we succeeded in isolating CHO mutants with an 85-95% reduced level of UV-induced DNA synthesis in combination with an increased UV sensitivity.

Animals↗
PubMed1982

Genetic heterogeneity in ataxia-telangiectasia studied by cell fusion.

The effect of x-rays on the rate of semiconservative DNA replication was investigated by autoradiography in single cells obtained from normal individuals and from patients having ataxia-telangiectasia (AT). In the five AT cell strains studied, the rate of DNA synthesis was inhibited to a lesser extent that in two normal cell strains. By using this abnormal regulation of DNA replication in AT cells as a marker, an experimental procedure was developed that allowed genetic complementation analysis of AT. After Sendai virus-induced fusion of AT cells, the grains were counted over binucleate cells with both nuclei in S phase. In some cases, the inhibition of DNA synthesis caused by x-rays in the heterodikaryons was more pronounced than that in the parental homodikaryons and was comparable to that in normal binucleate cells, indicating complementation. By using this approach, the five AT cell strains that were investigated could be assigned to three complementation groups. The data suggest that extensive genetic heterogeneity exists in AT.

Ataxia Telangiectasia↗
PubMed1982

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

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.

4-Nitroquinoline-1-oxide↗
PubMed1982

Genetic complementation analysis of ataxia telangiectasia by somatic cell fusion.

After cells from patients with ataxia telangiectasia (AT) have been exposed to ionizing radiation, the rate of semiconservative DNA replication is inhibited to a significantly lesser extent than in cells from normal individuals. This diminished inhibition of DNA synthesis is a general characteristic of irradiated AT cell strains, irrespective of their capacity to perform repair DNA synthesis after treatment with gamma-rays. Using the abnormal regulation of DNA replication in AT cells as a parameter, a procedure was developed that allows genetic complementation analysis of AT. The five AT cell strains that were investigated in this respect could be assigned to three complementation groups. The results show that an extensive genetic heterogeneity exists in the AT syndrome.

Ataxia Telangiectasia↗
PubMed1981

The rate of DNA synthesis in normal human and ataxia telangiectasia cells after exposure to X-irradiation.

The rate of DNA synthesis was studied in normal cell strains and in strains from patients suffering from the inherited disorder ataxia telangiectasia (AT). After exposure to relatively low doses of oxic X-rays (0-4 krad) DNA synthesis was depressed in AT cell strains to a significantly lesser extent than in normal cells. This response was observed in both an "excision-deficient" and an "excision-proficient" strain. In contrast, there was no difference in DNA-synthesis inhibition between AT and normal cells after UV exposure. After X-irradiation of cells from patients with xeroderma pigmentosum, both complementation group A and XP variants, the observed rate of DNA synthesis was equal to that in normal cells. An exception was the strain XP3BR which has been shown to be X-ray-sensitive. This strain exhibited diminished DNA synthesis inhibition after X-ray doses below 1 krad. These data suggest a relationship between hypersensitivity to X-rays and diminished depression of DNA synthesis.

Ataxia Telangiectasia↗
PubMed1980

Repair of DNA damage after exposure to 4-nitroquinoline-1-oxide in heterokaryons derived from xeroderma pigmentosum cells.

Xeroderma pigmentosum (XP) cells are deficient in the repair of damage induced by ultraviolet irradiation. Excision-repair-deficient XP cell strains have been classified into 7 distinct complementation groups, according to results of studies on cell fusion and UV irradiation. XP cells are not only abnormally sensitive to UV, but also to a variety of chemical carcinogens, including 4-nitro-quinoline-1-oxide (4NQO). Complementation analysis with XP strains from 4 different complementation groups with respect to the repair of 4NQO-induced DNA damage revealed that the classification of the strains into complementation groups with respect to 4NQO-induced repair coincides with the classification based on the repair of UV damage.

4-Nitroquinoline-1-oxide↗