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Biomedical subjects

R B Setlow

Publications and source records attributed to R B Setlow.

At least 109 records · Page 6Linked to original sources
PubMed1975

Direct evidence that pyrimidine dimers in DNA result in neoplastic transformation.

A specific test for the biological role of UV-induced pyrimidine dimers in DNA is photoreactivation (PR). Fish contain large amounts of the PR enzyme. Portions of cell suspensions of tissue from various organs of the fish Poecilia formosa were exposed to UV radiation (254 nm), then injected into isogenic recipients. An incident fluence of 20 J/m2 resulted in 10% of the fish with large granulomas and 100% with thyroid carcinomas. If the irradiated cell suspension was illuminated with PR light before injection, the yields of both types of lesion were reduced approximately 10-Fold. If the PR light was given before the UV exposure, there was no reduction in the numbers of growths. These experiments show that pyrimidine dimers in DNA can lead to neoplastic transformation.

Animals↗
PubMed1975

DNA repair and life span of mammals.

The ability of fibroblasts to perform unscheduled synthesis (a measure of excision-repair) after UV irradiation was measured autoradiographically for seven mammalian species at several times after UV irradiation. The initial rate and the maximum incorporation of [3H]dThd increased with the life span of the species.

Animals↗
PubMed1974

DNA repair in Potorous tridactylus.

The DNA synthesized shortly after ultraviolet (UV) irradiation of Potorous tridactylis (PtK) cells sediments more slowly in alkali than that made by nonirradiated cells. The size of the single-strand segments is approximately equal to the average distance between 1 or 2 cyclobutyl pyrimidine dimers in the parental DNA. These data support the notion that dimers are the photoproducts which interrupt normal DNA replication. Upon incubation of irradiated cells the small segments are enlarged to form high molecular weight DNA as in nonirradiated cells. DNA synthesized at long times ( approximately 24 h) after irradiation is made in segments approximately equal to those synthesized by nonirradiated cells, although only 10-15% of the dimers have been removed by excision repair. These data imply that dimers are not the lesions which initially interrupt normal DNA replication in irradiated cells. In an attempt to resolve these conflicting interpretations, PtK cells were exposed to photoreactivating light after irradiation and before pulse-labeling, since photoreactivation repair is specific for only one type of UV lesion. After 1 h of exposure approximately 35% of the pyrimidine dimers have been monomerized, and the reduction in the percentage of dimers correlates with an increased size for the DNA synthesized by irradiated cells. Therefore, we conclude that the dimers are the lesions which initially interrupt DNA replication in irradiated PtK cells. The monomerization of pyrimidine dimers correlates with a disappearance of repair endonuclease-sensitive sites, as measured in vivo immediately after 1 h of photoreactivation, indicating that some of the sites sensitive to the repair endonuclease (from Micrococcus luteus) are pyrimidine dimers. However, at 24 h after irradiation and 1 h of photoreactivation there are no endonuclease-sensitive sites, even though approximately 50% of the pyrimidine dimers remain in the DNA. These data indicate that not all pyrimidine dimers are accessible to the repair endonuclease. The observation that at long times after irradiation DNA is made in segments equal to those synthesized by nonirradiated cells although only a small percentage of the dimers have been removed suggests that an additional repair system alters dimers so that they no longer interrupt DNA replication.

Animals↗
PubMed1974

Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species.

The ability of fibroblasts to perform unscheduled DNA synthesis (a measure of excision-repair) after UV irradiation was measured radioautographically for seven species at several times after several UV fluences. Both the initial rate and the maximum incorporation of [(3)H]dThd increased with the life-span of the species (shrew, mouse, rat, hamster, cow, elephant, man). Unscheduled DNA synthesis was approximately proportional to the logarithm of life-span.

Aging↗
PubMed1974

The wavelengths in sunlight effective in producing skin cancer: a theoretical analysis.

DNA is taken as the target for skin cancer induced by ultraviolet light, and the known data on the sensitivity of DNA as a function of wavelength are summarized. The sun's spectrum at the surface of the earth and the DNA action spectrum are used to calculate the carcinogenic effectiveness as a function of wavelength. The most effective wavelengths at 30 degrees N latitude are <305 nm, and a 1% change in atmospheric ozone results in a 2% change in the effective dose of ultraviolet light. Since both the basic biological and physical data are reasonably precise, the major requirement for a quantitative evaluation of the dose response relation for ultraviolet-induced skin cancer in man is better epidemiological data to compare with data from animal models.

DNA↗
PubMed1973

Recovery of the ability to synthesize DNA in segments of normal size at long times after ultraviolet irradiation of human cells.

DNA synthesized in human cells within the first hour after ultraviolet (UV) irradiation is made in segments of lower molecular weight than in nonirradiated cells. The size of these segments approximates the average distance between pyrimidine dimers in the parental DNA. This suggests that the dimers interrupt normal DNA synthesis and result in gaps in the newly synthesized DNA. However, DNA synthesized in human cells at long times after irradiation is made in segments equal or nearly equal to those synthesized by nonirradiated cells. The recovery of the ability to synthesize DNA in segments of normal size occurs in normal human cells, where the dimers are excised, and also in cells of the human mutants xeroderma pigmentosum (XP), where the dimers remain in the DNA. This observation implies that the pyrimidine dimer may not be the lesion that causes DNA to be synthesized in smaller than normal segments.

Cell Line↗
PubMed1972

Repair replication in Escherichia coli as measured by the photolysis of bromodeoxyuridine.

The ability to selectively photolyze bromouracil-(BrUra-)containing repaired regions in cellular DNA has allowed us to estimate the average size of repaired regions in ultraviolet (UV) light-irradiated Escherichia coli. Cells were labeled with thymidine-(3)H, irradiated at 254 nm, and incubated in nonradioactive bromodeoxyuridine (BrdUrd). After incubation the cells were exposed to 10(6) ergs.mm(-2) at 313 nm, lysed, and sedimented in alkaline sucrose gradients so as to measure the average molecular weight of single DNA strands. In strains that had excised approximately 45 cyclobutane pyrimidine dimers/10(8) daltons, the 313 nm treatment resulted in approximately 6 single-strand breaks/10(8) daltons. In an excisionless strain, the same treatment resulted in only 1.5 breaks/10(8) daltons. From the determination of the sensitivities of fully substituted DNAs to 313 nm light, we calculate that the repaired regions in excising strains of E. coli contain an average of 4-6 BrUra residues. Photoreactivation experiments indicate that the excision of pyrimidine dimers in the presence of BrdUrd is the primary source of repaired regions selectively photolyzed by 313 nm radiation.

Bromodeoxyuridine↗