Ultraviolet Light Damage Research Articles

DeSanctis-Cacchione Syndrome

• One of the first patients studied by Cleaver on the DNA repair defect to ultraviolet light damage in xeroderma pigmentosum has been subjected to autopsy examination. This patient had the DeSanctis-Cacchione syndrome (microcephaly, dwarfism, mental deficiency, and choreoathetosis). Her autopsy findings were similar to those of the other three patients with this syndrome, emphasizing olivopontocerebellar atrophy, who underwent autopsy. The patient apparently could not tolerate psoralens because of increased incidence of carcinoma formation. (<i>Arch Dermatol</i>113:1561-1563, 1977)

Lack of repair of ultraviolet light damage in Mycoplasma gallisepticum

We have studied the repair capabilities of Mycoplasma gallisepticum, one of the smallest free-living cells, having a genome size of only 4.6 × 10 8 daltons. The data show that these cells have neither dark repair nor photoreactivation mechanisms for the repair of ultraviolet induced DNA damage. No other prokaryote has been reported to lack both kinds of repair systems. Studies of irradiated cell DNA indicate that the u.v.-induced pyrimidine dimers cannot be excised and block further replication. The photoreactivation experiments also showed that M. gallisepticum is photoinactivated.

Gap filling during postreplication repair of DNA in recombination deficient Escherichia coli

POSTREPLICATION repair of DNA is one pathway for repair of damage inflicted on DNA by physical and chemical agents in the environment1. Postreplication repair can involve error-prone repair of pyrimidine dimers in Escherichia coli2, and as such may be particularly relevant to the understanding of the alteration of initial damage in DNA to a transformed or mutant DNA. The assignment of gene products to essential roles for completion of postreplication repair gap filling after ultraviolet light (UV) damage in E. coli cells3–7 has been complemented by consideration of their respective roles in error-prone repair of UV damage8–11. We have used column chromatography, which separates double-stranded DNA containing single regions from completely double-stranded DNA, to observe the gap filling during postreplication repair of UV damage to DNA. In addition, analysis of E. coli recA or lex mutants demonstrated that the recA+ or the lex+ gene products must control steps exclusive of the initial gap filling process during postreplication repair.

Frequency of ultraviolet light-induced mutations is higher in xeroderma pigmentosum variant cells than in normal human cells.

PATIENTS with the inherited disease, xeroderma pigmentosum (XP), are subject to multiple carcinomas of the skin on areas exposed to sunlight1. Fibroblasts from the skin of the majority of these patients (classical XP) have been shown to be deficient in excision repair of lesions induced in DNA by ultraviolet radiation1–3. One group of patients, however, has been designated ‘XP variants’ because, although they suffer the clinical manifestations of the disease, they carry on normal excision repair of such ultraviolet-light damage to DNA4–6. Lehmann et al.6 reported that cells from such XP variants are abnormally slow in converting initially low molecular weight DNA, synthesised after ultraviolet irradiation, into high molecular weight DNA similar in size to that produced in unirradiated cells. Although these authors suggest that such abnormal DNA replication might explain why such patients are susceptible to cancer of the skin, they do not propose any mechanism. If the somatic cell mutation hypothesis on the origin of cancer, first suggested by Boveri7, is correct one would expect the frequency of mutations induced by ultraviolet light to be higher in cells derived from skin biopsies from both classical and variant XP patients than in cells from normal persons. To test this hypothesis, we have carried out a series of quantitative investigations comparing the frequency of ultraviolet-light induced mutations to azaguanine resistance in normal human skin fibroblasts with that found in various strains derived from classical and variant XPs. We have found that cells derived from both kinds of XP patients indeed show much higher frequencies than normal cells. The data comparing two classical XP strains with normal cells have been published8,9. Here, we present data obtained with variant strain, XP4BE.

Potentiation by caffeine of ultraviolet-light damage in cultured human cells

Five cultured human cell lines (T-1 kidney, Chang liver, H.Ep. No. 2, HeLa-S3 and HeLa-O) were irradiated with ultraviolet light and immediately exposed to 1.0 and 3.0 mM caffeine for 44 h thereafter. This caffeine treatment reduced the surviving fraction (assayed by colony formation) of the irradiated population, but did not significantly reduce the colony-forming ability of unirradiated control cells. These findings suggest that many cultured human cell lines exhibit post-UV potentiation of potentially lethal damage by caffeine.

Beta-alanine and adaptation in Drosophila

Populations of Drosophila melanogaster show melanistic polymorphism. Adult melanization is inversely related to the rate of incorporation of beta-alanine into tanning cuticles. Light tan pigmentation is directly related to this incorporation. Beta-alanine induced tanning serves to protect pupae from ultraviolet light damage. Flies which do not fail to incorporate injected beta-alanine into developing cuticles, but which exhibit inhibited beta-alanine synthesis (flies homozygous for the gene ‘b’) are not only protected, as pupae, from ultraviolet damage by beta-alanine injection but also show enhanced mating success when injected as newly emerged adults. The metabolic block in this mutant appears in the pathway from orotic acid through uracil to beta-alanine.

Ultraviolet Light Protection by Several New Compounds

The photoprotective capabilities of more than 30 compounds, many of which have not been used previously as ultraviolet light (UVL) protective agents, were studied by in vitro and in vivo testing. No correlation between in vitro and in vivo effectiveness was identified. Lack of effectiveness in one system does not preclude effectiveness in another. Many agents that imparted protection from x-radiation and UVL damage in vitro lacked topical efficacy in vivo. The in vivo protection from UVL achieved by most of the agents at clinical concentrations is a function of their ultraviolet absorption spectrum. Topical studies on humans showed that propyl gallate is a more effective protectant than the best known commercial sunscreen. It is nontoxic, almost nonstaining to fabric, and substantive to the epidermis. Unfortunately, it proved to be a strong contact sensitizer. Many clues to the unknowns in medicine are locked in the library, waiting for someone to open the right book at the right time. Alphonse Raymond Dochez 1882-1964

Cell Cycle Specific Recovery from Fractionated Exposures of Ultraviolet Light

Previous studies, using caffeine, have indicated that a deoxyribonucleic acid (DNA) synthesis period (S phase)-dependent potentiation of ultraviolet light (UV) damage occurs in mouse L cells, but the question remains whether this potentiation is due to a peculiar interaction of caffeine with irradiated cells or whether it is due to interference with a recovery process which can be demonstrated in the absence of the drug. To answer this question synchronized populations of L cells were exposed to various first exposures of UV. As a function of time after this initial exposure survival curves of cell colony-forming ability were determined. Results indicate that cells surviving the initial exposure delivered in G1 phase, which pass through S phase, show no effect of this exposure when irradiated in G2 phase. That is, the survival curve for such cells in G2 is the same as for cells irradiated in G2 phase which have not been irradiated in G1 phase. Conversely, cells which are exposed to UV in G2 phase and are ...

Increased resistance of DNA replication to ultraviolet light damage in amino acid-starved bacteria

Incubation of a log-phase culture of a ultraviolet light-resistant, tryptophanrequiring strain of Escherichia coli (B/r WP2) for 40 min without tryptophan allows completion of the DNA replication cycle. When this occurs before ultraviolet light exposure an increase in ultraviolet light resistance of the DNA replication system of 2-fold (in terms of target number) over the log phase culture is produced. The projection to the ordinate of the relative rate values for inhibition of DNA synthesis after a series of ultraviolet light doses gave a target number of 4 for the log phase culture and 8 for the amino acid-starved culture. A comparable increase in resistance to the lethal effect of ultraviolet light was also seen with the same preirradiation treatment. The data suggest the possibility that the same mechanism is responsible for both the decreased ultraviolet light lethality and decreased inactivation of DNA replication. Both are presumably produced by completion of the DNA replication cycle during amino acid starvation, since lack of thymine with a thymine-requiring substrain prevents the development of resistance.

Saturation of Dark Repair Synthesis: Accumulation of Strand Breaks

Reversal of ultraviolet light damage to DNA by the dark repair system is limited. Experiments utilizing density and radioactive labels demonstrated that repair synthesis is not proportional to dose at doses above 200 ergs/mm(2). In addition, the number of residual excision induced gaps in Escherichia coli B/r hcr(+) DNA increases with higher UV doses. The extent of repair is apparently limited by saturation of the repair synthesis step.

Evidence for Dark-Reactivation of Ultraviolet Light Damage in Mouse L Cells

The survival of colony-forming ability of mouse L cells after ultraviolet light (UVL) irradiation can be changed drastically by immediately incubating the cells in growth medium to which caffeine has been added. The nature of this effect is similar to previous results obtained by other workers for UVL-irradiated bacteria containing a dark-reactivation system. The nature of these similarities is as follows: The effect of caffeine on L cells is concentration-dependent in the range of 0.3 to 5 mM, and it is purely a postirradiation phenomenon, being dependent on the time after irradiation that caffeine is added to the cells. Cells incubated for one generation time in the absence of caffeine show no decreased colony-forming ability when incubated in its presence. The caffeine effect is not seen if the cells are exposed to ionizing radiation instead of UVL irradiation. Substitution of some of the thymine moieties of L cell DNA with BUdR sensitizes the cell to UVL, but when such cells are plated in the presence...

CHLOROPLAST “DISAPPEARANCE” AS A TOOL FOR STUDYING SOME EFFECTS OF ULTRAVIOLET LIGHT ON PLANTS*

SummaryWith certain precautions the “disappearance” of guard cell chloroplasts may serve as a quantitative measure of ultraviolet light damage to leaves.Irradiated French bean leaves are still appreciably photoreactivable after 30–60 min in darkness, but eventually they cease to be. This critical time is the same as with irradiated viruses photoreactivated in their hosts.Guard cells seem much less susceptible than other epidermal cells to damage by ultraviolet light because ultraviolet light doses 15 times as great as those that cause collapse of ordinary epidermal cells do not abolish reversible osmotic closure of stomata.