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R B Setlow

Publications and source records attributed to R B Setlow.

142 records · Page 8Linked to original sources

Photoreactivation in vivo of pyrimidine dimers in paramecium DNA.

Cells of Paramecium aurelia labeled with tritiated thymidine were irradiated with ultraviolet light and then were either exposed to photoreactivating light or kept in the dark as controls. In the controls, the level of thymine-containing pyrimidine dimers did not change, but in cells exposed to photoreactivating light such dimers were destroyed. This is the first demonstration in a eukaryote of in vivo photoreactivation of thymine-containing pyrimidine dimers.

Animals↗

Cyclobutane-type pyrimidine dimers in polynucleotides.

The formation of cyclobutane-type dimers between adjacent pyrimidine residues in model polynucleotides or DNA may be represented by the general scheme See pdf 379.pdf Whereas the formation of all other known photoproducts follows the irreversible path See pdf 379.pdf Thus dimers are distinguished from other photoproducts by the fact that they can be monomerized, as well as formed, by ultraviolet irradiation. At large incident fluxes of photons the steady-state value of dimers depends on wavelength and pH, as well as on other characteristics of the surrounding medium. The number of dimers in an irradiated polynucleotide may be decreased by purely photochemical means, whereas this is not true for most other photoproducts, for which continued irradiation, irrespective of wavelength, always results in the formation of more photoproduct (37). The wavelength dependence of the steady-state for dimers is also reflected in the biological activity of irradiated transforming DNA. This experiment and the fact that photoreactivating enzyme plus visible light monomerizes dimers (and has not been demonstrated to have any effect on other photoproducts) are the strongest lines of experimental evidence that pyrimidine dimers of the cyclobutane type are biologically important lesions and can account for a large fraction of the effects of ultraviolet light on DNA in solution. Insofar as DNA is one of the more important biological structures, such dimers, when formed, account for a large part of the effects of ultraviolet radiation on biological systems.

Chemical Phenomena↗

DNA repair in late-passage human cells.

Monolayer cultures of WI-38 cells from passages 18 to 60 were exposed to ultraviolet radiation, or to N-acetoxy-AAF, or to gamma-rays. The cultures were incubated in 3H-dThd, and unscheduled DNA synthesis--a measure of DNA repair--was measured radioautographically. Late passage cultures showed less repair, and many cells showed none. Double-label radioautographs indicated that there is an excellent correlation between cells that do scheduled synthesis and cells that do unscheduled synthesis. We interpret our results as indicating that failure of repair is not a causal event in the failure of late passage cells to divide, but that as cells age the ability to do the many coordinated steps in repair declines.

Acetoxyacetylaminofluorene↗

Spontaneous and induced micronuclei and UDS in peripheral lymphocytes.

We have examined the distributions both of spontaneous and X-ray-induced micronuclei (MN) and of spontaneous and UV-induced unscheduled DNA synthesis (autoradiographic grains; UDS) in cultures of peripheral blood lymphocytes from normal, healthy human volunteers. While the spontaneous MN and UDS do not differ significantly from the expected Poisson distributions, both the induced MN and UDS are strongly overdistributed (i.e., variance much greater than mean). This not only must be allowed for in statistical tests used for population monitoring, but offers suggestive evidence that there are large differences in radiation response from sample to sample, some of which may reflect true differences among normal, healthy subjects.

Adult↗

O6-methylguanine-DNA methyltransferase in lymphocytes of the elderly with and without Alzheimer's disease.

Deficiency in DNA repair has been linked to aging, mutagenesis, carcinogenesis and several types of primary neuronal degeneration. O6-Methylguanine-DNA methyltransferase is a key enzyme in the repair of DNA alkylation damage that removes a methyl group from the O6 position of methylguanine. This study was carried out to determine whether there were any changes in the activity of this enzyme in lymphocytes of patients with Alzheimer's disease (AD) as compared to lymphocytes of age-matched non-demented elderly. The transferase activity in lymphocytes from 19 elderly patients with AD (mean 87.7 fmole/100 micrograms protein +/- SD 44.7) was not statistically different from that in 19 age/sex-matched controls (mean 91.3 fmole/100 micrograms protein +/- SD 40.0). There was no significant trend with age in transferase activity and the activity levels in the elderly subjects studied were the same as those reported previously for younger individuals by this laboratory. It is concluded that a reduction in O6-methylguanine-DNA methyltransferase activity is unlikely to be involved in the etiology or the pathogenesis of AD.

Age Factors↗