There is convincing evidence that cellular prooxidant states--that is, increased concentrations of active oxygen and organic peroxides and radicals--can promote initiated cells to neoplastic growth. Prooxidant states can be caused by different classes of agents, including hyperbaric oxygen, radiation, xenobiotic metabolites and Fenton-type reagents, modulators of the cytochrome P-450 electron-transport chain, peroxisome proliferators, inhibitors of the antioxidant defense, and membrane-active agents. Many of these agents are promoters or complete carcinogens. They cause chromosomal damage by indirect action, but the role of this damage in carcinogenesis remains unclear. Prooxidant states can be prevented or suppressed by the enzymes of the cellular antioxidant defense and low molecular weight scavenger molecules, and many antioxidants are antipromoters and anticarcinogens. Finally, prooxidant states may modulate the expression of a family of prooxidant genes, which are related to cell growth and differentiation, by inducing alterations in DNA structure or by epigenetic mechanisms, for example, by polyadenosine diphosphate-ribosylation of chromosomal proteins.

https://science.sciencemag.org/content/sci/227/4685/375.full.pdf

Prooxidant states and tumor promotion.

Background Nonmelanoma skin cancer (NMSC) is the most common cancer affecting white-skinned individuals and the incidence is increasing worldwide. Objectives This systematic review brings together 75 studies conducted over the past half century to look at geographical variations and trends worldwide in NMSC, and specifically incidence data are compared with recent U.K. cancer registry data. Methods Following the development of a comprehensive search strategy, an assessment tool was adapted to look at the methodological quality of the eligible studies. Results Most of the studies focused on white populations in Europe, the U.S.A. and Australia; however, limited data were available for other skin types in regions such as Africa. Worldwide the incidence for NMSC varies widely with the highest rates in Australia [>1000/100, 000 person-years for basal cell carcinoma (BCC)] and the lowest rates in parts of Africa ( Conclusions NMSC is an increasing problem for health care services worldwide. This review highlights a requirement for prevention studies in this area and the issues surrounding incomplete NMSC registration. Registration standards of NMSC should be improved to the level of other invasive disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2133.2012.10830.x

A systematic review of worldwide incidence of nonmelanoma skin cancer.

Collagen and elastin networks make up the majority of the extracellular matrix in many organs, such as the skin. The mechanisms which are involved in the maintenance of homeostatic equilibrium of these networks are numerous, involving the regulation of genetic expression, growth factor secretion, signalling pathways, secondary messaging systems, and ion channel activity. However, many factors are capable of disrupting these pathways, which leads to an imbalance of homeostatic equilibrium. Ultimately, this leads to changes in the physical nature of skin, both functionally and cosmetically. Although various factors have been identified, including carcinogenesis, ultraviolet exposure, and mechanical stretching of skin, it was discovered that many of them affect similar components of regulatory pathways, such as fibroblasts, lysyl oxidase, and fibronectin. Additionally, it was discovered that the various regulatory pathways intersect with each other at various stages instead of working independently of each other. This review paper proposes a model which elucidates how these molecular pathways intersect with one another, and how various internal and external factors can disrupt these pathways, ultimately leading to a disruption in collagen and elastin networks.

/pdf/molecular-mechanisms-of-stress-responsive-changes-in-27n4lb5raa.pdf

Molecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin

Stratospheric ozone levels are near their lowest point since measurements began, so current ultraviolet-B (UV-B) radiation levels are thought to be close to their maximum. Total stratospheric content of ozone-depleting substances is expected to reach a maximum before the year 2000. All other things being equal, the current ozone losses and related UV-B increases should be close to their maximum. Increases in surface erythemal (sunburning) UV radiation relative to the values in the 1970s are estimated to be: about 7% at Northern Hemisphere mid-latitudes in winter/spring; about 4% at Northern Hemisphere mid-latitudes in summer/fall; about 6% at Southern Hemisphere mid-latitudes on a year-round basis; about 130% in the Antarctic in spring; and about 22% in the Arctic in spring. Reductions in atmospheric ozone are expected to result in higher amounts of UV-B radiation reaching the Earth's surface. The expected correlation between increases in surface UV-B radiation and decreases in overhead ozone has been further demonstrated and quantified by ground-based instruments under a wide range of conditions. Improved measurements of UV-B radiation are now providing better geographical and temporal coverage. Surface UV-B radiation levels are highly variable because of cloud cover, and also because of local effects including pollutants and surface reflections. These factors usually decrease atmospheric transmission and therefore the surface irradiances at UV-B as well as other wavelengths. Occasional cloud-induced increases have also been reported. With a few exceptions, the direct detection of UV-B trends at low- and mid-latitudes remains problematic due to this high natural variability, the relatively small ozone changes, and the practical difficulties of maintaining long-term stability in networks of UV-measuring instruments. Few reliable UV-B radiation measurements are available from pre-ozone-depletion days. Satellite-based observations of atmospheric ozone and clouds are being used, together with models of atmospheric transmission, to provide global coverage and long-term estimates of surface UV-B radiation. Estimates of long-term (1979-1992) trends in zonally averaged UV irradiances that include cloud effects are nearly identical to those for clear-sky estimates, providing evidence that clouds have not influenced the UV-B trends. However, the limitations of satellite-derived UV estimates should be recognized. To assess uncertainties inherent in this approach, additional validations involving comparisons with ground-based observations are required. Direct comparisons of ground-based UV-B radiation measurements between a few mid-latitude sites in the Northern and Southern Hemispheres have shown larger differences than those estimated using satellite data. Ground-based measurements show that summertime erythemal UV irradiances in the Southern Hemisphere exceed those at comparable latitudes of the Northern Hemisphere by up to 40%, whereas corresponding satellite-based estimates yield only 10-15% differences. Atmospheric pollution may be a factor in this discrepancy between ground-based measurements and satellite-derived estimates. UV-B measurements at more sites are required to determine whether the larger observed differences are globally representative. High levels of UV-B radiation continue to be observed in Antarctica during the recurrent spring-time ozone hole. For example, during ozone-hole episodes, measured biologically damaging radiation at Palmer Station, Antarctica (64 degrees S) has been found to approach and occasionally even exceed maximum summer values at San Diego, CA, USA (32 degrees N). Long-term predictions of future UV-B levels are difficult and uncertain. Nevertheless, current best estimates suggest that a slow recovery to pre-ozone depletion levels may be expected during the next half-century. (ABSTRACT TRUNCATED)

Changes in biologically active ultraviolet radiation reaching the Earth's surface

Objectives To estimate the incidence of nonmelanoma skin cancer (NMSC) in the US population in 2006 and secondarily to indicate trends in numbers of procedures for skin cancer treatment. Design A descriptive analysis of population-based claims and US Census Bureau data combined with a population-based cross-sectional survey using multiple US government data sets, including the Centers for Medicare and Medicaid Services Fee-for-Service Physicians Claims databases, to calculate totals of skin cancer procedures performed for Medicare beneficiaries in 1992 and from 1996 to 2006 and related parameters. The National Ambulatory Medical Care Service database was used to estimate NMSC-related office visits. We combined these to estimate totals of new skin cancer diagnoses and affected individuals in the overall US population. Results The total number of procedures for skin cancer in the Medicare fee-for-service population increased by 76.9% from 1 158 298 in 1992 to 2 048 517 in 2006. The age-adjusted procedure rate per year per 100 000 beneficiaries increased from 3514 in 1992 to 6075 in 2006. From 2002 to 2006 (the years for which the databases allow procedure linkage to patient demographics and diagnoses), the number of procedures for NMSC in the Medicare population increased by 16.0%. In this period, the number of procedures per affected patient increased by 1.5%, and the number of persons with at least 1 procedure increased by 14.3%. We estimate the total number of NMSCs in the US population in 2006 at 3 507 693 and the total number of persons in the United States treated for NMSC at 2 152 500. Conclusions The number of skin cancers in Medicare beneficiaries increased dramatically over the years 1992 to 2006, due mainly to an increase in the number of affected individuals. Using nationally representative databases, we provide evidence of much higher overall totals of skin cancer diagnoses and patients in the US population than previous estimates. These data give the most complete evaluation to date of the underrecognized epidemic of skin cancer in the United States.

https://jamanetwork.com/journals/jamadermatology/articlepdf/209782/dst90063_283_287.pdf

Incidence Estimate of Nonmelanoma Skin Cancer in the United States, 2006

Recent reports of stratospheric ozone depletion have prompted concerns about the levels of solar ultraviolet radiation that reach the earth9s surface. Since 1974 a network of ground-level monitoring stations in the United States has tracked measurements of biologically effective ultraviolet radiation (UVB, 290 to 330 nanometers). The fact that no increases of UVB have been detected at ground levels from 1974 to 1985 suggests that meteorological, climatic, and environmental factors in the troposphere may play a greater role in attenuating UVB radiation than was previously suspected.

https://science.sciencemag.org/content/sci/239/4841/762.full.pdf

Biologically effective ultraviolet radiation: surface measurements in the United States, 1974 to 1985

A survey of the incidence of non-melanoma skin cancer was undertaken in four areas which included about ten million people. Complete reporting of all newly diagnosed cases of skin cancer which occurred during the survey period of September 1, 1971 to February 29, 1972 was obtained by canvassing dermatologists, radiotherapists, pathologists, and other physicians seeing and treating skin cancer. Rates among Caucasians were found two to three times higher than any ever reported before in these area. An estimate of 300,000 new cases of skin cancer per year would amount to about one-half the total for all other forms of cancer combined in the United States. In all areas, there was an excess liability in males of about 2 to 1. Highest rates were observed in the Dallas-Ft. Worth area, where increased solar radiation is suspected as a carcinogenic agent.

Non-melanoma skin cancer among Caucasians in four areas of the United States.

Fluoroquinolone antibacterials are known to be phototoxic, both in vivo and in vitro. The action spectrum for the phototoxicity of the quinolones lies mainly in the UVA region. During studies of systemic drug phototoxicity, Johnson et al. (Dundee) induced dose-dependent phototoxicity in Swiss albino mice, and severe phototoxic reactions were followed by the development of skin tumors. The present study was designed to compare the ability of several quinolones to produce photobiologic effects following chronic, subphototoxic UVA radiation. To compare the activities of different quinolones (lomefloxacin, fleroxacin, ciprofloxacin, ofloxacin and nalidixic acid), doses that result in similar plasma and skin levels of drug were administered by gavage to slightly pigmented Skh-1 hairless mice for up to 78 weeks. 8-Methoxypsoralen (8-MOP) was used as a positive control, and unirradiated, drug-treated and irradiated and unirradiated drug-free controls were also used. No signs of phototoxicity were seen, except for minimal-to-slight erythema and swelling of the skin in animals of the lomefloxacin-UVA group. Skin tumors (1 mm in diameter or larger) were observed in all the irradiated groups and the incidence was increased in all the groups treated with the test articles. The cumulative tumor prevalence was accelerated, the median latent periods were shortened and tumor onset was significantly enhanced by 8-MOP plus UVA, lomefloxacin plus UVA and fleroxacin plus UVA, as compared with vehicle plus UVA-exposed animals. The majority of skin tumors (with the exception of lomefloxacin and 8-MOP) were benign. The majority of squamous cell carcinomas in the lomefloxacin group were of a histologic type different from those previously reported in UVA-exposed animals. Thus, all the fluoroquinolone antibiotics studied have the capability of enhancing UVA-induced phototumorigenesis, but only lomefloxacin caused the development of cystic squamous cell carcinomas in the majority of treated animals.

Fluoroquinolone antibacterials enhance UVA-induced skin tumors

• The relative importance of risk factors such as solar exposure, complexion, age, and the ability to tan were examined for their relationships to the development of basal and squamous cell carcinoma. Three samples were studied: patients with basal cell carcinoma (N = 366), patients with squamous cell carcinoma (N = 58), and control subjects (N = 294). The technique of logistic regression was used to estimate the relative risk of each type of carcinoma. Solar exposure was the most important risk factor for both basal and squamous cell carcinoma; however, the ability to tan was shown to be of special importance even at low levels of exposure. Given the same level of cumulative lifetime solar exposure, subjects over 60 years of age were shown to be at higher risk for nonmelanoma carcinoma than those at younger ages. Complexion was only shown to be significant for basal cell carcinoma. ( Arch Dermatol 116:454-456, 1980)

Frederick Urbach

Papers

Biologically effective ultraviolet radiation: surface measurements in the United States, 1974 to 1985

Non-melanoma skin cancer among Caucasians in four areas of the United States.

Fluoroquinolone antibacterials enhance UVA-induced skin tumors

The relative importance of risk factors in nonmelanoma carcinoma.

Incidence of nonmelanoma skin cancer.