PROJECTIONS OF INCREASED NON-MELANOMA SKIN CANCER INCIDENCE DUE TO OZONE DEPLETION

Abstract— Projections of increase in non-melanoma skin cancer incidence due to ozone layer depletion by chlorofluorocarbons are presented. Projections have been made for five different ozone depletion scenarios, based on US. Environmental Protection Agency estimates of potential worldwide industrial production and commercial applications of chlorofluorocarbons, and their eventual release into the atmosphere. The least favorable scenario, a regulatory cap on production at estimated 1990 levels, would lead to an eventual 30% ozone depletion and to an eventual doubling of skin cancer incidence by the year 2300. The most favorable scenario, a reduction in production commencing now and reaching a low production target by 1990, would limit ozone depletion to an eventual 2.8%, and increase in skin cancer to about 5%. Compared to the least favorable scenario, the most favorable one would prevent an average of about 100,000 cases of skin cancer per year in the United States between now and the year 2100.     

SKIN CANCER AND ULTRAVIOLET RADIATION

Abstract. A new model is presented for the calculation of the increased incidence of non-melanoma skin cancer in Caucasians resulting from ozone reduction. The model postulates that the probability of first incidence of such skin cancer is distributed log-normally as a function of total accumulated lifetime dose of harmful ultraviolet radiation. The effect on skin cancer incidence of an increase in harmful ultraviolet radiation due to ozone reduction can then be calculated directly from the extent to which each individual's lifetime accumulated dose is thereby increased. The result of such a perturbation, on average, would be to cause skin cancer to appear at a slightly earlier age. Since skin cancer is predominantly a disease of the elderly, this shift to younger ages has the effect, when integrated over the entire population, of increasing the overall total incidence of skin cancer.     

STRATOSPHERIC OZONE DEPLETION BETWEEN 1979 and 1992: IMPLICATIONS FOR BIOLOGICALLY ACTIVE ULTRAVIOLET-B RADIATION and NON-MELANOMA SKIN CANCER INCIDENCE

Abstract— The depletion of stratospheric ozone (0₃) has predictable implications for increases in biologically damaging solar ultraviolet-B radiation (UVB,280–320 nm) reaching the earth's surface. A radiative transfer analysis of satellite-based O₃ measurements between January 1979 and December 1992 shows that surface UVB levels increased substantially at all latitudes except the tropics, if other factors such as cloud cover and local pollutant levels have remained constant over this period. Exposure to UVB radiation is known to induce basal cell and squamous cell skin cancers, and dose-response relationships derived from epidemiological data can be combined with the UVB enhancements to estimate the seasonal and latitudinal distribution of future expected increases in the incidence of these cancers.     

POTENTIAL EFFECTS OF ALTERED SOLAR ULTRAVIOLET RADIATION ON HUMAN SKIN CANCER

There is highly significant evidence that non-melanoma skin cancers are primarily due to chronic repeated exposure to solar ultraviolet radiation, and that there is a significant, although somewhat different relationship between solar radiation and the development of cutaneous malignant melanoma. Recent experimental and epidemiologic studies show that the biologically most effective UVR wavelengths are in the segment of the solar UVR spectrum that would be significantly augmented by decreases in stratospheric ozone content. A recent report on measurements of column ozone changes in the stratosphere has shown that in the past 18 yrs, there has been an ozone decrease between 2 and 3%, greater in the winter months, and somewhat differing with latitude in the Northern Hemisphere. Calculations of the relationship of ozone decrease to increase in biologically effective UVR show great dependence on the biologic action spectrum assumed. Based on extensive epidemiologic studies of skin cancer incidence, it appears that the estimated increase in biologically effective UVR due to the measured ozone decreases in the past (almost) two decades are not likely to be the cause of the sharp increase in skin cancer incidence which have been observed. Most likely these increases in incidence are the result of increasing personal exposure, due to striking changes in personal behavior that have taken place for social reasons. However, there is every reason to believe that increases in biologically effective UVR due to stratospheric ozone decreases will have significant impact on human skin cancer incidence in the future.     

THE OCULAR DOSE OF ULTRAVIOLET RADIATION FROM SUNLIGHT EXPOSURE

Abstract— The ocular toxicity of ultraviolet radiation has been demonstrated in acute photokeratitis and is suspected of contributing to cataractogenesis and senile macular degeneration. While previous studies have emphasized photochemical and epidemiologic aspects of ocular UV-B irradiation, little is known about the extent of such exposure in human subjects. To determine levels of ocular UV-B exposure from sunlight, four mannikin headforms were fitted with UV-B sensitive film (polysulphone) and exposed on an unobstructed rooftop (Baltimore, Md.: latitude = 39.5 degrees) to four hours of sunlight (11 am-3 pm local time) over a three month period (June-August). Simultaneous measurements of ocular and ambient exposure revealed a ratio of 19.5 ± 2.9% that was independent of ambient level (P < 0.05). Measurements performed during earlier hours (8 am-11 am) revealed a similar ratio. Mannikin headforms fitted with brimmed baseball caps showed a22–95% reduction in ocular exposure, depending on the angle of the hat brim to the forehead. Three sets of spectacles substantially reduced ocular UV-B exposure,62–94% dependent on the absorption properties of the spectacle lenses. These anthropomorphic measurements indicate that a substantial percentage of ambient UV-B light is incident upon the cornea and that personal factors, such as wearing a hat or spectacles, can markedly affect UV-B exposure.     

THE VASCULAR RESPONSE OF HUMAN SKIN TO ULTRAVIOLET RADIATION

The vascular response of human skin to 300 nm (UV-B) and 254 nm (UV-C) ultraviolet radiation was assessed using the reflectance measurement of erythema and the technique of laser Doppler velocimetry. For both wavelengths, the increase in measured Doppler blood flux varied with the increase in erythema in a quadratic manner predicted by a simple model based on the principles of fluid mechanics. This suggests that the mean red blood cell velocity increases significantly in areas of UV-B and UV-C erythema. No qualitative difference in response to these two wavelengths was demonstrated, suggesting that the same blood vessels are involved in the causation of both UV-B and UV-C erythema.     

ENHANCEMENT OF MUTAGENESIS AND HUMAN SKIN CANCER RATES RESULTING FROM INCREASED FLUENCES OF SOLAR ULTRAVIOLET RADIATION

Abstract— We present a new method for calculating the effects of reduction of atmospheric ozone upon induction of nonmelanoma skin cancer. These estimates are based upon several recent experimental improvements: a model for the atmospheric penetration of UV-B; measurements of the transmission of this radiation by human epidermis; a precise action spectrum for genetic effects (mutation) in Escherichia coli , which was corrected for finite slit width. The calculated radiation amplification factor or percent increase in exposure per one percent decrease in atmospheric ozone is constant at 1.7 for solar zenith angles = 70° and decreases only with larger values of this angle. Thus the estimated increase applies to all heavily populated areas. of the globe. The value is robust: it is almost the same when the albedo is reduced from 0.2 to 0.1 or when the epidermal transmission is assumed to be about fourfold greater.     

ULTRAVIOLET RADIATION AND SKIN CANCER: IN MICE AND MEN*

Abstract— In both mice and men the effects of repeated exposures to UVR accumulate. Unresolvable uncertainty pertains in both cases. Incidence of skin cancer in human populations may be influenced by various factors that cannot be separately evaluated. Uncertainty of predictions regarding the effect of increased UVR due to diminution of stratospheric ozone cover is discussed.     

THE WAVELENGTH DEPENDENCE OF HERPES SIMPLEX VIRUS INACTIVATION BY ULTRAVIOLET RADIATION

The effect of different wavelengths of ultraviolet (UV) radiation on Herpes simplex virus when assayed on mammalian cells (measured by plaque forming ability) was investigated. The wavelength dependence of viral inactivation was obtained for 11 different wavelengths over the region 238–297 nm. The resulting action spectrum does not closely follow the absorption spectrum of either nucleic acid or protein. The most effective wavelengths for viral inactivation are over the region 260–280 nm.     

THE WAVELENGTH DEPENDENCE OF ULTRAVIOLET ENHANCED REACTIVATION IN A MAMMALIAN CELL-VIRUS SYSTEM

Abstract— The effect of UV radiation in the wavelength region 230 nm to 302 nm on the ability of an irradiated mammalian cell to reactivate UV-irradiated mammalian virus was tested. An action spectrum for radiation enhanced reactivation (RER) is presented. The shape of the action spectrum points to a combined nucleic acid-protein target for UV radiation effects on this cellular parameter. An analysis of the results of others involving the biochemical and photobiological events involved in RER does not allow us to distinguish which macromolecule is the major contributor to this effect. Studies involving an analogous phenomenon in bacteria (Weigle reactivation) imply that RER and WR may involve similar mechanisms.     

THE WAVELENGTH DEPENDENCE OF ULTRAVIOLET INACTIVATION OF HOST CAPACITY IN A MAMMALIAN CELL-VIRUS SYSTEM

Abstract. The ability of UV-irradiated African green monkey kidney cells (CV-1) to support the growth of unirradiated herpes simplex virus type 1 as measured by plaque forming ability has been investigated. The lowering of plaque formation by the virus when the host cell was irradiated was examined at thirteen different wavelengths. An action spectrum for this cellular parameter (capacity) was obtained in the wavelength region of 235–302 nm. This action spectrum points to nucleic acid as the critical target molecule for this effect.     

EFFECTS OF DOSE FRACTIONATION ON ULTRAVIOLET SURVIVAL OF ESCHERICHIA COLI

Abstract— Exposure of E. coli B/r and B at low average dose rates of u.v. radiation (2537 Å), produced either by fractionated doses or by continuous irradiation at a very low dose rate (80 ergs/mm²/hr), results in much increased survival compared to single exposure at high dose rate. This increase is attributed to repair taking place during the irradiation period. The effect is small in the repair-deficient strains E. coli B_8-1_, and C syn- , and is absent in phage T1 and T4, which cannot undergo repair in the extracellular state. However, the prolonged time available for repair in these experiments accounts for only a very minor part of the increase in survival. The principal factor apparently is that the number of lesions present at any time remains relatively low. Presumably complete repair, not only the excision step, can occur in buffer during the irradiation period. This interpretation is supported by experiments in which cells were exposed to combinations of highly fractionated irradiation and single-dose irradiation. We therefore propose that mutual interference in repair, possibly by overlapping of repair regions in complementary DNA strands, reduces considerably the repair efficiency if many lesions are present. This hypothesis explains the 'shouldered' survival curves of B/r and possibly other E. coli strains as due to decreasing repair efficiency with increasing u.v. dose     

INDUCTION OF SKIN TUMORS IN THE RAT BY SINGLE EXPOSURE TO ULTRAVIOLET RADIATION

Abstract— The dose response for tumor induction in albino rat skin by single exposures of UV radiation has been characterized. The shaved dorsal skin of 202 animals was exposed to either of two sources: one emitting a broad spectrum of wavelengths from 275 to 375 nm, and the other emitting at 254 nm. Skin tumors began to appear within 10 weeks of exposure and continued to appear for 70 weeks. The highest tumor yield was 5.5 tumors per rat and occurred when the rats were exposed to 13.0 times 10⁴ J/m² of the 275–375 nm UV. The 275–375 nm UV was about eight times as effective as the 254 nm UV for the induction of tumors throughout the exposure range from 0.8 times 10⁴ to 26.0 times 10⁴J/m². Tissue destruction and hair follicle damage was found at the highest exposure to 275–375 nm UV but at none of the exposures to 254 nm UV. Repeated weekly exposures to 275–375 nm UV proved less effective than an equivalent single exposure for inducing tumors, even though the multiple exposures caused more severe skin damage. The transmission of the UV through excised samples of rat epidermis indicated that the exposure to the basal cell layer was about 3% of the surface exposure at 254 nm and about 15% of the surface exposure between 275 and 320 nm. The dependence of tumor yield on UV exposure was linear for 254 nm UV but was more complex for the 275–375 nm UV. For the latter more tumors were produced per unit exposure at lower exposures than at higher exposures.     

WAVELENGTH DEPENDENCE OF DNA INCISION BY A HUMAN ULTRAVIOLET ENDONUCLEASE

The wavelength dependence of an ultraviolet irradiation of the DNA substrate for a human endonuclease was determined. Sites of DNA incision for all UVB and UVC wavelengths examined were at cytosines which were neither cyclobutane pyrimidine dimers nor 6-4'-(pyrimidin-2-one)pyrimidines. The optimal wavelengths for formation of these cytosine photoproducts were between 270 and 295 nm. This human endonuclease therefore has a similar ultraviolet substrate specificity to endonuclease III.     

EVALUATION OF SKIN CANCER RISK RESULTING FROM LONG TERM OCCUPATIONAL EXPOSURE TO RADIATION FROM ULTRAVIOLET LASERS IN THE RANGE FROM 190 TO 400 nm

The relative risk of occupational exposure to radiation from UV lasers was estimated using a mathematical model based on both epidemiological data and animal experiments. Calculations were performed for the 193 nm ArF excimer laser cornea shaping, the 308 nm XeCl excimer laser for coronary angioplasty, and other UV lasers in a laboratory environment. The model included the effects of direct exposure and exposure to scattered radiation. The results show that for the two medical applications the increase in the relative risk is comparable to that of one additional day of sunbathing per year. For subjects exposed to UV lasers in a laboratory setting, the relative risk may increase to a value comparable to that of people with an outdoor profession.     

WAVELENGTH DEPENDENCE OF THE FORMATION OF SINGLE-STRAND BREAKS AND BASE CHANGES IN DNA BY THE ULTRAVIOLET RADIATION ABOVE 150 nm

The wavelength dependence of the formation of two types of DNA damage, single-strand breaks and base changes, was investigated in the UV region from 150 nm to 254 nm using superhelical closed circular (form I) colicin El DNA with synchrotron radiation. Single-strand breaks were measured by agarose gel electrophoresis as a direct conversion of form I DNA to form II DNA (open circular). Base damages were defined as sensitive sites to a crude extract of endonuclease from Micrococcus luteus. They also were estimated using the same conversion, from form I to form II after the DNA was treated with endonuclease. The fluence-effect relationship could be fitted by a simple exponential function for both types of damage. Action spectra were constructed based on the reciprocal of the 37% fluence. The action spectrum for strand breaks increased rather monotonically over three decades from 254 nm to 150 nm in a logarithmic scale, while that for base damages showed a breaking point at 190 nm, being relatively flat above 190 nm. The characteristics of the action spectra are compared with the absorption spectra of the DNA and its main chain moiety calculated on the basis of data on calf thymus DNA and synthetic polynucleotides. Our main conclusions are (1) that the majority of single-strand breaks were induced by the absorption of photon in the sugar-phosphate group in the vacuum-UV region and (2) that the base changes were induced equally well by absorption in the vacuum-UV and in the far-UV region.     

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 photoimmunological 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 (290–400nm) were greater than two-fold higher than those for unfiltered FS20 sunlamp UV (250–400nm). Xenon arc solar simulator UV (295–400nm) 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 (250–290nm) 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.