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Biomedical subjects

R B Setlow

Publications and source records attributed to R B Setlow.

At least 37 records · Page 2Linked to original sources
PubMed1993

DNA damage, photorepair, and survival in fish and human cells exposed to UV radiation.

The effect of various wavelengths of UVB radiation on the induction of cyclobutane pyrimidine dimers in fish cells and human fibroblasts and the repair of these lesions were studied using an UV-endonuclease to measure dimers (endonuclease sensitive sites) by sedimentation of radioactive DNA, by gel electrophoresis of unlabeled DNA, and by cell survival. The data show that fish cells have an efficient photoreactivation system at wavelength > 304 nm that reverses cytotoxicity and dimer formation after exposure to filtered sunlamp irradiation of a shorter wavelength (lambda > 290 nm). Shorter wavelengths in UVB (> 304 nm) are more effective in photoreversal than longer ones (> 320 nm). As a consequence, 50-85% of dimers induced by these wavelengths in fish are photoreactivated while they are being formed. A major cytotoxicological lesion is the cyclobutane pyrimidine dimers. Cultured human fibroblasts do not possess such a repair system. These results indicate that sunlamp irradiation has wavelengths that both damage and repair DNA.

Animals↗
PubMed1991

X-ray sensitivity of fibroblast cell strains derived from atomic bomb survivors with and without breast cancer.

Fibroblasts were established in vitro from skin biopsies obtained from 55 women and 1 man with or without breast cancer and with or without exposure to radiations from the atomic bomb (A-bomb) explosion in Hiroshima. The radiosensitivity of these cells was evaluated by clonogenic assays after exposure to X-rays. Dose-response curves were fitted to a multitarget model, S/S0 = A[1-(1-e-D/D0)N]. There was no difference in the means or variances of radiosensitivity between exposed and nonexposed groups, or between groups with and without breast cancer.

Breast Neoplasms↗
PubMed1990

Radiosensitivity of skin fibroblasts from atomic bomb survivors with and without breast cancer.

Fibroblasts were established in vitro from skin biopsies obtained from 55 women and 1 man with or without breast cancer and with or without exposure to radiation from the atomic bomb explosion in Hiroshima. The radiosensitivity of these cells was evaluated by clonogenic assays after exposure to X-rays or to fission neutrons from a 252Cf source. Data were fitted to a multitarget model, S/S0 = A [1 - (1 - ekD)N], for both X-ray and neutron dose-survival curves. A single hit model, S/S0 = AekD, fits the neutron dose-survival responses as well. There were no differences in the means or variances of radiosensitivity between exposed and nonexposed groups or between patients with or without breast cancer. Hence, although the sample is not large, it provides no support for the hypothesis that atomic bomb radiation preferentially induces breast cancer in women whose cells in vitro are sensitive to cell killing by radiation.

Adolescent↗
PubMed1989

Animal model for ultraviolet radiation-induced melanoma: platyfish-swordtail hybrid.

Sunlight exposure is strongly indicated as one of the important etiologic agents in human cutaneous malignant melanoma. However, because of the absence of good animal models, it has not been possible to estimate the wavelengths or wavelength regions involved. We have developed a useful animal model from crosses and backcrosses of platyfish (Xiphophorus maculatus) and swordtails (Xiphophorus helleri). Two strains of these fish are susceptible to invasive melanoma induction by exposure to filtered radiation from sunlamps in the wavelength ranges lambda greater than 290 nm and lambda greater than 304 nm. Multiple exposures on 5-20 consecutive days beginning on day 5 after birth or a single exposure of approximately 200 J/(m2.day) of lambda greater than 304 nm result in a tumor prevalence of 20% to 40% at 4 months of age compared with a background rate of 12% in one strain and 2% in another. Exposure of the fish to visible light after UV exposure reduces the prevalence to background. The melanomas are similar in many respects to mammalian melanomas, as judged by light and electron microscopy. The genetics of the crosses determined by others and the high sensitivity of the hybrids to melanoma induction indicate that the UV radiation probably inactivates the one tumor repressor gene (or a small number of tumor repressor genes) in the hybrid fish. The small size of the animals and their high susceptibility to melanoma induction make them ideal for action spectroscopy.

Animals↗
PubMed1989

Inactivation of O6-alkylguanine-DNA alkyltransferase in HeLa cells by cisplatin.

Inactivation of O6-alkylguanine-DNA alkyltransferase (O6-AGT) in HeLa CCL2 cells by cisplatin was studied. HeLa CCL2 cells treated with cisplatin showed a dose-dependent decline in O6-AGT activity. After cisplatin was removed and replaced with fresh medium, the transferase level began to rise slowly. By 72 h slightly more than 80% of the activity was recovered. It seems that the activity of the alkyltransferase can be inactivated by platinated DNA adducts. The data suggest that the O6-platinum-guanine formation and the O6-alkyltransferase depletion are not responsible for cytotoxicity but may result in a base substitution mutation in mammalian cells.

Cell Survival↗
PubMed1987

DNA repair by articular chondrocytes. IV. Measurement of Micrococcus luteus endonuclease-sensitive sites by alkaline elution in rabbit articular chondrocytes.

The ability of resting and dividing rabbit articular chondrocytes to repair low doses of ultraviolet (UV) damage was measured through removal of UV endonuclease-sensitive sites (ESS, pyrimidines dimers) as measured by alkaline elution. The repair of damage was significantly (P less than 0.001) greater in dividing than non-dividing cells. An age-related decrease in repair capability was found in resting chondrocytes, but not in their dividing counterpart. These results support earlier findings of unscheduled DNA synthesis by the same cells. (Mech. Ageing Dev., 32: 39-55, 1985).

Animals↗
PubMed1987

DNA repair by articular chondrocytes. V. O6 methylguanine-acceptor protein activity in resting and cultured rabbit and human chondrocytes.

The level of O6-methylguanine acceptor protein activity was examined in rabbit and human articular chondrocytes of different ages. The activity per microgram of DNA in rabbit chondrocytes was 5-fold lower than in humans. There was no age-dependent decrease in the activity of resting or cultured chondrocytes of either species. The values for resting cells were comparable to those of cultured cells. The lack of age-related differences in methyltransferase activity, in contrast to nucleotide excision repair [Mech. Ageing Dev. 32 (1985) 39-55], indicates that separate repair systems behave differently with respect to chronological aging. The methyl transferase activity may be more essential for survival of articular chondrocytes and therefore more highly conserved with age.

Aging↗
PubMed1986

Quantitation of radiation-, chemical-, or enzyme-induced single strand breaks in nonradioactive DNA by alkaline gel electrophoresis: application to pyrimidine dimers.

We have developed an alkaline agarose gel method for quantitating single strand breaks in nanogram quantities of nonradioactive DNA. After electrophoresis together with molecular length standards, the DNA is neutralized, stained with ethidium bromide, photographed, and the density profiles recorded with a computer controlled scanner. The median lengths, number average molecular lengths, and length average molecular lengths of the DNAs can be computed by using the mobilities of the molecular length standards. The frequency of single strand breaks can then be determined by comparison of the corresponding average molecular lengths of DNAs treated and not treated with single strand break-inducing agents (radiation, chemicals, or lesion-specific endonuclease). Single strand break yields (induced at pyrimidine dimer sites in uv-irradiated human fibroblasts DNA by the dimer-specific endonuclease from Micrococcus luteus) from our method agree with values obtained for the same DNAs from alkaline sucrose gradient analysis. The method has been used to determine pyrimidine dimer yields in DNA from biopsies of human skin irradiated in situ. It will be especially useful in determining the frequency of single strand breaks (or lesions convertible to single strand breaks by specific cleaving reagents or enzymes) in small quantities of DNA from cells or tissues not amenable to radioactive labeling.

DNA Damage↗