Action Spectra for Killing Non‐dividing Normal Human and Xeroderma Pigmentosum Cells

Kantor, George J.; Sutherland, John C.; Setlow, R. B.

doi:10.1111/j.1751-1097.1980.tb03728.x

Cited by 55 publications

(27 citation statements)

References 19 publications

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“…The sensitivity of the cells for lethality was also wavelength dependent and lower at the longer wavelengths. The shape of the survival curves was also similar to those found in other action spectra studies utilizing mammalian cells (19,20).…”

supporting

confidence: 72%

Ultraviolet light action spectra for neoplastic transformation and lethality of Syrian hamster embryo cells correlate with spectrum for pyrimidine dimer formation in cellular DNA.

Doniger¹,

Jacobson²,

Krell³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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Action spectra were determined for neoplastic transformation, production of pyrimidine dimers, and lethality in Syrian hamster embryo cells. Ofwavelengths between 240 and 313 nm, the most effective were 265 and 270. The relative sensitivities per quantum for transformation, pyrimidine dimer production, and lethality were essentially the same at each of the wavelengths tested. This action spectrum for transformation, which is relevant to carcinogenesis, is similar to spectra obtained previously by measuring other cellular responses in either microbial or mammalian systems.. Because the action spectra for cytotoxicity and transformation are the same as the spectrum for dimer production, DNA.is suggested as the target for all these processes. The positive relationship between exposure to sunlight and incidence of skin cancer in humans has been well established (1-3). Photocarcinogenesis studies utilizing albino mice have shown 300-320 nm to be the most effective range for producing tumors in mice (4). Wavelengths shorter than 300 nm are less effective in inducing tumors because they are absorbed by the upper layers of the epidermis.The spectral irradiance of sunlight at the earth's surface is essentially constant at wavelengths longer than 330 nm and decreases by more than 4 orders of magnitude between 330 nm and 290 nm (5). The precise spectrum for a given place and time depends on the angle of incidence of sunlight, the meteorological conditions, and the thickness of the ozone layer. Environmental factors that decrease the ozone layer can increase the intensity ofwavelengths shorter than 330 nm at the earth's surface and consequently could increase the incidence of skin cancer in man. A theoretical analysis ofthe wavelengths in sunlight effective in producing skin cancer was developed by Setlow (6) to correlate the possible effects of changing the ozone layer on the incidence of skin cancer. An average action spectrum for effects of UV on bacterial systems (see below) was used as an estimate in Setlow's analysis because no action spectrum for carcinogenesis was available. An action spectrum for transformation utilizing mammalian cells would eliminate the need to extrapolate from bacterial models.In early studies, the relationship between the biological and biochemical effects of UV were pursued by using microbial systems. Pyrimidine dimers, the major UV-induced photoproduct in DNA, are considered to be responsible for most of the biological effects such as cell lethality and mutation (7). Studies of UV action spectra were instrumental in implicating nucleic acid as the chromophore for killing bacteria (8, 9) and bacteriophages (10) and for mutation in fungi (11). DNA was further implicated as the target.for lethality and mutation because the action spectrum for pyrimidine dimer formation (12, 13) was found to be similar to that for killing.The in vitro transformation of Syrian hamster embryo cells (HEC) by carcinogens is a model system for studying carcinogenesis in a quantitative manner (14). DiPaolo ...

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supporting

confidence: 72%

Ultraviolet light action spectra for neoplastic transformation and lethality of Syrian hamster embryo cells correlate with spectrum for pyrimidine dimer formation in cellular DNA.

Doniger¹,

Jacobson²,

Krell³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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“…Other stages of development display a potentiation of UV lethality with anisomycin but are unaffected by actinomycin D. Similarly, increasing the period of dark incubation following irradiation leads to an increase in cell survival. These results are in contrast to the effect of "liquid holding," which shows a gradual decrease in UV associated lethality [13,16]. These results indicate that the resistance of the gonidia is a direct measure of the effect of UV at the time of irradiation and that this resistance is a function of the activity of the repair system(s).…”

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confidence: 74%

Developmental changes in the sensitivity of Volvox to ultraviolet light

Baran

Huskey

1985

Dev. Genet.

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The response of Volvox to ultraviolet irradiation was analyzed. Young individuals isolated from a synchronous culture were exposed to UV light (120 J/m2) and subjected to variable length periods of dark following irradiation. The major effect of the UV treatment was the inability of the gonidia present in the colonies at the time of irradiation to continue and complete the developmental program. Individuals show a heightened sensitivity to UV for a limited period immediately following inversion and are insensitive at other stages of development. The cytotoxic effect of UV during this interval is completely reversed by the immediate exposure to white light and is increased with longer periods of dark treatment prior to exposure to white light. The temporal profile of the sensitivity defines a smooth curve in which the maximal sensitivity occurs three hours after inversion. The response to higher doses of UV (up to 500 J/m2) is a nonlinear increase in cytotoxicity and is disproportionately greater in those individuals just prior to the period of maximal sensitivity than those later in development. The results suggest that Volvox has at least two pathways for the repair of UV damage and that one of these, the principal dark repair pathway, is temporarily deficient in the gonidia of young individuals.

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“…However, action spectra for dimer formation in cells and killing (25), mutation, and transformation (5) of human and other eukaryotic cells show small but significant differences from the absorption spectrum of mammalian DNA (26).…”

Section: Discussionmentioning

confidence: 99%

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light.

Freeman

Hacham

Gange

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

287

172

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The UV components of sunlight are believed to be a major cause of human skin cancer, and DNA is thought to be the principal molecular target. Alterations of the intensity and wavelength distribution of solar UV radiation reaching the surface of the earth, for example by depletion of stratospheric ozone, will change the effectiveness of solar radiation in damaging DNA in human skin. Evaluation of the magnitude of such effects requires knowledge of the altered sunlight spectrum and of the action spectrum for damaging DNA in human skin. We have determined an action spectrum for the frequency of pyrimidine dimer formation induced in the DNA of human skin per unit dose of UV incident on the skin surface. The peak of this action spectrum is near 300 nm and decreases rapidly at both longer and shorter wavelengths. The decrease in our action spectrum for wavelengths <300 nm is attributed to the absorption of the upper layers of the skin, an in situ effect that is inherently included in our measurements. Convolution of the dimer action spectrum with the solar spectra corresponding to a solar angle of 40' under current levels of stratospheric ozone (0.32-cm 03 layer) and those for 50% ozone depletion (0.16-cm 03 layer), indicate about a 2.5-fold increase in dimer formation. If the action spectrum for DNA damage that results in skin cancer resembles that for dimer induction in skin, our results, combined with epidemiological data, suggest that a 50% decrease in stratospheric ozone would increase the incidence of nonmelanoma skin cancers among white males in Seattle, Washington, by 7.5-to 8-fold, to a higher incidence than is presently seen in the corresponding population of Albuquerque, New Mexico.Sunlight causes erythema, premature aging, and cancers in human skin (1), and several lines ofevidence indicate that UV radiation of wavelengths <320 nm is of primary importance in damage induction (2). Studies of the wavelength dependence of carcinogenesis in mouse skin (3) and of erythema induction in human skin (4) indicate that the efficiency of damage induction by photons in the wavelength range 290-400 nm varies strikingly. Thus, alteration of the solar spectrum reaching the earth's surface-for example, through alteration in the ozone content of the stratosphere-will affect the frequency of DNA damages, including those in human skin.Quantitative prediction of the extent of damage and of its biological consequences requires convolution of the altered solar spectrum with the action spectrum for inducing human skin cancer (2). Because this action spectrum is not known, other biological response functions have been used to approximate the human skin cancer spectrum: action spectra (i) for carcinogenesis in mouse skin (3), (ii) for killing and mutation in prokaryotes (2), and (iii) for killing, mutation, and transformation of mammalian cells in culture (5, 6), as well as several different action spectra (iv) for erythema in human skin (4, 7). However, the optical properties of mouse skin and of prokaryotes and mammalian ...

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Action Spectra for Killing Non‐dividing Normal Human and Xeroderma Pigmentosum Cells

Cited by 55 publications

References 19 publications

Ultraviolet light action spectra for neoplastic transformation and lethality of Syrian hamster embryo cells correlate with spectrum for pyrimidine dimer formation in cellular DNA.

Ultraviolet light action spectra for neoplastic transformation and lethality of Syrian hamster embryo cells correlate with spectrum for pyrimidine dimer formation in cellular DNA.

Developmental changes in the sensitivity of Volvox to ultraviolet light

Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light.

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