Study of Pyrimidine Dimers in Mammalian Cells Surviving Low Doses of Ultraviolet Radiation*

Trosko, James E.; Kasschau, Margaret R.

doi:10.1111/j.1751-1097.1967.tb08806.x

Cited by 69 publications

(12 citation statements)

References 14 publications

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“…There is no detectable excision of UV-induced pyrimidine dimers in mouse and hamster cells, and presumably rodent cells in general (14,24,25). If the decrease in U1-U5 snRNA synthesis observed in human cells within 2 h after UV irradiation were somehow related to the removal of pyrimidine dimers, one might not expect to see it in mouse cells.…”

Section: Resultsmentioning

confidence: 99%

Sensitivity to UV radiation of small nuclear RNA synthesis in mammalian cells.

Eliceiri¹,

Smith²

1983

Mol. Cell. Biol.

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It was demonstrated previously that the synthesis of small nuclear RNA (snRNA) species Ut and U2 in human cells is very sensitive to UV radiation. In the present work, the UV sensitivity of U3, U4, and U5 snRNA synthesis is shown to be also high. The synthesis of Ut, U2, U3, U4, and U5 snRNAs progressively decreased during the first 2 h after UV irradiation (this was not observed in polyadenylated RNA) and had not returned to normal rates 6 h after UV exposure. In contrast, the restoration of 5.8S rRNA synthesis began immediately after UV irradiation and was essentially complete 6 h later. A small fraction of Ut and U5 (and possibly U2 and U3) snRNA synthesis remained unaffected by high UV doses, when cell radiolabeling began 10 min after UV irradiation. The present data suggest that a factor other than the level of pyrimidine dimers in DNA (possibly, steps in the post-irradiation DNA repair process) plays an important role in the mechanism of UV-induced inhibition of U1-U5 snRNA synthesis.UV radiation causes random formation of pyrimidine dimers in DNA, which result in premature termination of transcription (23). This effect has been used to determine the length of transcription units, since the probability of causing a UV lesion within a transcription unit is directly proportional to its length. Human Ut and U2 small nuclear RNA (snRNA) synthesis is very sensitive to UV radiation (4), suggesting that the UV target sizes of Ut and U2 snRNAs are much larger than those of the known precursors to these snRNAs (5). In contrast, the synthesis of small RNAs whose primary transcripts are not much longer than those of the mature species, like 4S and 5S RNA, is not affected by the same dose range of UV radiation (4, 8). Mammalian snRNA species Ul, U2, U3, U4, and U5 share several common properties, including having N2,N2,7-trimethylguanosinecapped structures at their 5' ends (3) and possibly being synthesized by RNA polymerase II (5, 7, 9, 12, 21, 22; S. C. Chandrasekharappa, J. H. Smith, and G. L. Eliceiri, J. Cell. Physiol., in press). The original goal of the present work was to determine whether U3, U4, and U5 snRNA synthesis is also sensitive to UV radiation; our results show that it is. Ul through U5 snRNA synthesis decreases during the first 2 h after UV irradiation and is not restored to normal levels for at least 6 h after UV exposure. These results t Present address: Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada N6A SB7.suggest that a factor other than the pyrimidine dimer content of DNA is important in the UV inhibition of U1-U5 snRNA synthesis.MATERIALS AND METHODS KB or HeLa (human) cells, grown in spinner culture, were exposed to UV light as described earlier (at 15 cm from a GE G2578 lamp) (4). After specified times in spinner culture at 37°C, the cells were labeled with [3H]uridine (40 p.Ci/ml) for 40 min, except for the experiment in Fig. 1 and 2 where labeling was for 80 min. The radioactive medium was removed, and the cells were incubated for 2 h in fresh medium su...

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Section: Resultsmentioning

confidence: 99%

Sensitivity to UV radiation of small nuclear RNA synthesis in mammalian cells.

Eliceiri¹,

Smith²

1983

Mol. Cell. Biol.

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“…photoproducts in DNA. Selective release of pyrimidine dimers from u.v.-irradiated Chinese hamster cells into acid-soluble products has not been demonstrated (table 1; Trosko, Chu andCarrier 1965, Trosko andKasschau 1967). On the basis of the arguments presented above, we conclude that most of the products we detected were due to degradation of DNA subsequent to the release of nucleolytic enzymes from killed cells.…”

Section: Discussionmentioning

confidence: 62%

“…light (Boyce and Howard-Flanders 1964, Aoki, Boyce and HowardFlanders 1966, Clark, Chamberlain, Boyce and Howard-Flanders 1966, or x-rays (McGrath, Williams andSchwartzendruber 1966, Pollard andWeller 1968). In contrast, irradiated mammalian cells undergo very little DNA degradation (Cleaver 1968, Little 1968, Painter 1968, Watanabe and Okada 1968. In neither bacteria nor mammalian cells has the nature of these degradation products been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

DNA-degradation Products from Mammalian Cells Irradiated with Ultra-violet Light

Cleaver

Trosko

1969

International Journal of Radiation Biology and Related Studies

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Chinese hamster cells begin to die and degrade their DNA within 6 to 8 hours after 140 erg/mm 2 and 700 erg/mm 2 of u.v. light. Cell lysis releases macromolecular double-strand DNA and DNA degradative enzymes into the medium. Extracellular DNA degradation leads to an accumulation of thymidine and thymine in the medium. Intracellular degradation also occurs, and the acidsoluble fraction of the cells contains polynucleotides, phosphorylated derivatives of thymidine and thymine. Specific excision of thymine dimers in an acidsoluble form does not occur, and the contribution of DNA repair mechanisms to the observed degradation products is probably insignificant. No detectable amounts of DNA-degradation products (i.e. less than 005 per cent of total cellular DNA) were used for post-irradiation DNA synthesis.

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“…The early work from Dick Setlow's laboratory and in our laboratory suggested that permanently established mouse and hamster cells in culture were very defective in repair [Klimek, 1966;Painter and Cleaver, 1969;Trosko et al, 1965;Trosko and Kasschau, 1967]. Despite these early studies, it proved possible to develop many UV-sensitive mutants of hamster cells [Thompson et al, 1980], showing they had a functional NER system.…”

Section: Are Rodent Cells Really Repair-deficient?mentioning

confidence: 99%

Richard B. Setlow, a commentary on seminal contributions and scientific controversies

Cleaver

2001

Environ and Mol Mutagen

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Richard B. Setlow inspired the field of DNA repair. His demonstration that photoproducts could be quantified within cells and their excision examined experimentally pioneered the identification of nucleotide excision repair. His early work was associated with the discovery of many founding phenomena of photobiology and DNA repair: the concept of excision repair itself, correlations between DNA repair, life span and aging, variations in repair among mammalian species, caffeine sensitization to UV damage, and the xeroderma pigmentosum (XP) repair deficiencies. We may now have mapped thoroughly the landscape of DNA repair that Dick helped open to exploration, but questions persist of how comprehensively we have explored all its canyons and mesas. Research into nontraditional species and kingdoms may yet provide unexpected surprises. The signal transduction pathways and mechanisms of DNA replication arrest in damaged mammalian cells remain a challenge. The importance of repair in vivo also provides many difficult research questions. One problem of current interest is the role of endogenous DNA damage and repair in human pathology, especially neurodegeneration exemplified by many XP patients. Cancer and neurodegeneration may represent converse responses of dividing and nondividing cells to mutagenic and lethal effects of DNA damaging agents. Cell death from endogenous oxidative DNA damage (apoptosis) may be antagonistic to malignant transformation in dividing cells but may cause neurodegeneration in nondividing neural tissue. Small reductions in the efficiency of repair, especially transcription-coupled repair, may overemphasize carcinogenesis in mice, while minimizing neurodegeneration, as compared to human patients.

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Study of Pyrimidine Dimers in Mammalian Cells Surviving Low Doses of Ultraviolet Radiation*

Cited by 69 publications

References 14 publications

Sensitivity to UV radiation of small nuclear RNA synthesis in mammalian cells.

Sensitivity to UV radiation of small nuclear RNA synthesis in mammalian cells.

DNA-degradation Products from Mammalian Cells Irradiated with Ultra-violet Light

Richard B. Setlow, a commentary on seminal contributions and scientific controversies

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