UV Dose Response Research Articles

Minimum doses of ultraviolet radiation required to induce murine skin edema and immunosuppression are different and depend on the ultraviolet emission spectrum of the source.

Many photo immunological studies have used UV radiation sources that emit nonsolar UV spectral energy and UV doses based on nonimmunological endpoints, e.g. erythema and skin edema. Interpretation of these data has led to misunderstanding when extrapolated to hypothetical effects in humans exposed to solar UV. The purpose of this study was to: (1) establish UV dose response relationships for murine skin edema and immunosuppression, and (2) determine how different UV spectra affect these relationships. Back skin and ear minimum edema doses (MEdD) for Kodacel-filtered FS20 sunlamp UV (290-400 nm) were greater than two-fold higher than those for unfiltered FS20 sunlamp UV (250-400 nm). Xenon are solar simulator UV (295-400 nm) MEdD were > 10-fold higher than those for unfiltered sunlamp UV. Back skin and ear MEdD differed two- to five-fold between C3H/HeN, SWR/J and HRA/Skh-1 mice. The minimum immunosuppression doses (MISD) in C3H mice showed similar UV source spectrum dependence. The solar simulator UV MISD was 5.4- and 1.5-fold higher than for unfiltered and Kodacel-filtered sunlamp UV MISD, respectively. Furthermore, MISD were from 3- to 50-fold higher than the MEdD for the three UV sources. The UV bioeffectiveness spectra indicated that UVC energy (250-290 nm) contributed 12% and 18%, respectively, of the total skin edema and immunosuppression UV energy. These data demonstrate the variability in UV sensitivity among mouse strains, the significant differences between murine MEdD and MISD and how these differences are influenced by nonsolar regions (below 295 nm) of the UV spectrum.

Repair of UV Damage in Actively Transcribed Ribosomal Genes

Repair of UV-induced cyclobutane pyrimidine dimers (CPDs) was measured in the individual strands of transcriptionally active ribosomal genes in mouse Friend erythroleukemia cells. Ribosomal genes (rDNA) are multicopied, but only a fraction is transcriptionally active (or transcriptionally "poised"). Selective psoralen binding was used to separate the active fraction, which has an open chromatin structure, from inactive rDNA. EcoRI digestion was used to selectively release the active fraction from nuclei for DNA repair studies. UV dose response curves indicate there is no significant bias for CPD formation in either strand of both types of rDNA chromatin. More importantly, there was no evidence for transcription repair coupling in the individual strands of active and total rDNA. Indeed, over an 8 h period (one cell-cycle), repair of CPDs was almost nonexistent in either strand of active and total rDNA. Furthermore, the fraction of each chromatin structure remains constant during these repair times, suggesting that chromatin rearrangements observed during excision repair of nonnucleolar chromatin do not occur following UV damage of rDNA. However, CPDs are removed efficiently from the transcribed strand of the constitutively expressed c-abl gene (transcribed by Pol II), demonstrating that these cells are capable of transcription repair coupling.

Enhanced development of murine melanoma in UV-irradiated skin: UV dose response, waveband dependence, and relation to inflammation

Previously we reported that exposure of mice to UV radiation increases the incidence of melanomas arising from injection of syngeneic melanoma cells into the UV-irradiated ears. In this study, we investigated the UV dose-response characteristics, duration, waveband dependence, and role of inflammation in this effect of UV irradiation. The optimal conditions consisted of short term (3-4 weeks), intermittent (twice weekly) exposures to a moderate dose (4.8 kJ/m2) of UVB (280-320 nm) radiation from FS40 sunlamps and the effect lasted only for 3 days after the final UV irradiation. Removal of wavelengths below 315 nm with a Mylar filter abrogated the effect. The UV dose response and the time course of UV-induced inflammation, assessed by ear swelling and microscopic evaluation, did not correlate with that for enhanced melanoma outgrowth, nor did the treatment of the ears with the inflammatory agents turpentine and 12-o-tetradecanoyl phorbol-13-acetate mimic the UV effects on melanoma development. These results indicate that enhancement of melanoma development in UV-irradiated skin is probably unrelated to the inflammatory effects of UV irradiation.

Polyacetylene content and UV‐induced 6‐methoxymellein accumulation in carrot cultivars

AbstractThe antifungal polyacetylenes falcarindiol and falcarinol, the production potential of the phytoalexin 6‐methoxymellein (6‐MM), and the carbohydrate profiles of five carrot cultivars were studied in order to assess variability in their content of these compounds as well as to determine the existence of any interrelationship among them. The polyacetylene content was measured in the peel of carrot roots shortly after harvest; the accumulation of 6‐MM was measured in carrot slices incubated at 1°C after exposure to ultraviolet light (UV‐C); and the carbohydrate content (glucose, fructose, sucrose and total non‐structural), determined on whole carrots. Significant differences among the cultivars were noted in the content of polyacetylenes and 6‐MM accumulation as well as in the carbohydrate constituents. The variation among the cultivars for the polyacetylene content and that for the accumulation of 6‐MM were found to be independent of each other. The results suggest that cultivars with higher levels of antifungal compounds could be bred in order to improve their resistance to diseases. The carbohydrate profiles of the cultivars did not affect their production of 6‐MM. Furthermore, 6‐MM accumulation–UV dose response was similar for all the cultivars. Thus, a single dose of UV could be used to induce 6‐MM in several cultivars of carrot.

Abnormal mutation frequencies in human repair-defective hybrid cell lines

Two intraspecific human cell hybrids, HD2 and HD1A, produced from fusion between HeLa cells and xeroderma pigmentosum fibroblasts, express XPD-like rates of excision repair and hypersensitivity to UV-radiation. In the present paper we described unusual patterns of UV-induced mutation in both cell lines. Though HD2 very closely resembles XPD both phenotypically and genetically, in UV-dose response it is hypomutable at the loci for ouabain and diphtheria toxin resistance. At equitoxic dose, however, it shows normal mutability, HD1A, by contrast, is hypermutable as a function either of UV dose or in terms of equitoxicity for these genes. HD1A's mutator phenotype is a dominant characteristic and is not associated with grossly abnormal DNA precursor pool imbalance. The possibility remains that DNA polymerase infidelity underlies its hypermutability.

Role of Solar Conditioning in DNA Repair Response and Survival of Human Epidermal Keratinocytes Following UV Irradiation

We have investigated the cumulative effects of sunlight exposure upon the excision-repair of UV radiation damage to DNA in epidermal keratinocytes from human donors of different ages as well as the possible effect on DNA repair of periodic conditioning of the cultured keratinocytes with sublethal UV radiation exposures. We have also compared the growth properties of UV-irradiated keratinocytes derived from habitually sun-exposed and nonexposed areas from the bodies of young and aged donors. DNA repair replication in keratinocytes from habitually sun-exposed facial skin and the less sun-exposed abdominal skin of middle-aged adults was found to be similar, with respect to both the UV dose response and the time course of repair after 20 J/m2, 254 nm. Growth and survival (after exposure up to 50 J/m2, 254 nm) were greater for keratinocytes from protected areas of the upper arm of young donors (under 18 years) than for cells from their own sun-exposed areas. Growth and survival were markedly reduced for all keratinocyte cultures from aged donors, especially those cultures developed from sun-exposed areas. Nevertheless, the DNA repair response to UV radiation was similar in all cases. The evident uncoupling of UV sensitivity from DNA repair capacity remains to be understood. Our studies confirm that the cumulative effect of sunlight exposure indeed contributes to some skin aging processes. However, we have found no indication that an overall reduction in capacity for excision-repair of UV photoproducts in keratinocyte DNA accompanies senescence in human skin.

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 γ-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 consequence of the way such cells handle DNA damage caused by ionizing radiation.