Causes and Effects of Stratospheric Ozone Reduction An Update (1982) / Chapter Skim
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3 MOLECULAR AND CELLULAR STUDIES
3 MOLECULAR AND CELLULAR STUDIES
Pages 47-61
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From page 47... ...
However, despite the similarity between the DNA action spectrum and the action spectra for killing, mutating, or transforming mammalian cells in culture, irradiation of such cellular systems with broad bands of radiation does not give results that would be predicted from the sum of the effects at discrete wavelengths. There are good indications that the longer wavelengths in W-B, or W-A, may modify the effects of UV-B.
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From page 48... ...
Preliminary estimates indicate that photoreactivation is very rapid in humans and takes place to an appreciable extent even while human skin is being irradiated by the W-B in sunlight. Consequently, the level of pyrimidine dimers in cellular DNA in viva depends upon the relative intensities of the dimer-forming wavelengths in UV-B and the dimer-splitting wavelengths in UV-A and visible radiation.
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From page 49... ...
There were no reliable action spectra for W effects on mammalian cells, and there was a good possibility that the correct action spectrum might be different from that for bacterial DNA, because in higher organisms DNA is not a naked polymer but is closely associated with proteins. This association might change the action spectrum and might give rise to other deleterious photoproducts, for example, cross-links between protein and DNA.
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From page 50... ...
Excision repair is a very active process in normal human cells. Cells from individuals with a genetically inherited, sunlight-sensitive, cancer-prone disease called xeroderma pigmentosum are in almost all cases defective in excision repair.
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From page 51... ...
of W-transformed rodent cells are usually tumorigen~c when injected into certain mouse strains, but no tumori genicity has been shown for the W-transformed human cells described in the experimental results shown in Figure 3.1. Transformation of mouse and hamster cells is accomplished by single acute doses of W , but transforma tion of human cells thus far has only been effected by several small W doses (Sutherland et al.
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From page 52... ...
The killing of frog cells is photoreversed with equal effectiveness at each damage-producing wavelength tested between 252 nm and 313 nm (Rosenstein and Setlow 1980) , and transformation of human cells by W -B is photoreactivable (Sutherland et al.
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From page 53... ...
The action spectrum for dimer formation itself is a complicated function of wavelength since all types of pyrimidine dimers may be formed, such as thymine-thymine, thymine-cytosine, and cytosine-cytosine. The ratio of cytosine-thymine to thymine-thymine dimers appears to increase with wavelength from 290 nm to 313 nm (Ellison and Childs 1981)
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From page 54... ...
Thus for monochromatic radiation sources and the effects shown in Figure 3.1, almost all cells follow the DNA action -- not absorption -- spectrum. The primary conclusion drawn from the current understanding of action spectra is that all have similar shapes and hence the DNA action spectrum for mammalian cells may be taken to represent an average spectrum (not drawn in the figure)
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From page 55... ...
. These data indicate that normal human skin has both an active excision repair process and an active photoreactivation process, as was inferred from experiments on cells in culture (see the section below, "Mitigation and Enhancement of W -B Effects by Light at Other Wavelengths")
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From page 56... ...
If the suppression of these immune responses is important in UV carcinogenesis, and if their biological sensitivities at longer wavelengths are greater than that for damage to DNA, the effects of ozone depletion would be less than those computed for a DNA action spectrum. This is because it is the steepness of the action spectrum in the UV-B that makes ozone depletion important (see Figure 2.2)
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From page 57... ...
Among the known antagonistic processes are photoreactivation and photoprotection. Photoreactivation was defined earlier as a process in which UV-A or visible light eliminates the pyrimidine dimers produced by UV-B.
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From page 58... ...
Such synergisms may operate in the sunlight induction of skin cancer in those humans whose skin is defective in error-free repair systems, such as those with excision-defective xeroderma pigmentosum (Maher and McCormick 1976)
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From page 59... ...
At present, the quantitative response to an enhancement in UV intensity in the region of 305 nm to 310 nm as a result of ozone depletion, with the other, longer UV wavelengths remaining constant, is not known. There is some evidence for the existence of UV-induced repair systems in mammalian cells (Bockstahler and Lytle 1977, Rommelaere et al.
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From page 60... ...
Irradiation of cells before virus infection results in an enhanced survival of the infecting W-irradiated viruses, and in some instances a higher frequency of mutations is observed in irradiated viruses infecting irradiated cells (Des Gupta and Summers 1978)
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From page 61... ...
The aim of such studies would be to determine whether the kinetics of dark repair of damage from dimers in human skin show two components, a slow and a fast one, as is true for human cells irradiated in vitro. (The fast component represents repair of DNA in the so-called linker regions of chromatic, and the slow reaction is the repair in the core regions of chromatin (Cleaver 1977, Smerdon et al.
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