Exposure of nondividing populations of primary human fibroblasts to UV (254 nm) radiation induces a transient enhancement in capacity to repair potentially lethal cellular damage.

Abstract

Nondividing (arrested) populations of primary human fibroblasts from normal individuals exposed to an initial dose (1.5 or 3 J m-2) of far-UV (254 nm) radiation and then incubated in medium containing low (0.5%) serum develop enhanced resistance to inactivation of cloning efficiency by a second (challenge) dose of UV. The resistance develops within 2-4 days, after which there is a decline. Resistance develops to a higher degree and more rapidly (1-2 days) in cells derived from patients with the variant form of xeroderma pigmentosum. Excision-deficient cells from xeroderma pigmentosum complementation group A individuals also develop UV resistance after a lower (0.2 J m-2) exposure to UV. Enhanced UV resistance does not develop in UV-irradiated cell populations incubated with the protein synthesis inhibitor cycloheximide (5 IPM). These observations are consistent with the interpretation that exposure of human fibroblasts to low doses of UV induces synthesis of a protein involved in a metabolic pathway that transiently enhances the capacity of cells to repair potentially lethal damage resulting from a subsequent dose of UV.The genetic control and biochemistry of an error-prone far-UV inducible repair system in Escherichia coli has been extensively studied (see ref. 1 for overview). Recent experiments have begun to clarify the nature of the inducing signal (2) and enzymology (3) of the process. The existence of a similar phenomenon in eukaryotic cells has been largely inferred from viral reactivation studies (4). The survival of many types of UV-damaged virus is enhanced by pre-exposure of the appropriate host cells to UV radiation and incubation for an appropriate time prior to viral infection (see ref.5 for review). The nature and degree of error-proneness of the response, as deduced from enhanced mutagenesis of infecting virus (6, 7), appears to vary considerably with the particular virus and host cell system employed. For example, the mutability of intact but not UV-irradiated parvovirus H1 is enhanced in UV pretreated human or rat cells (8), whereas only enhanced mutability of UV-treated virus is seen when simian virus 40 infects UV-treated monkey cells (7). Findings opposite to the latter have been reported (9, 10).Biochemical measurements of UV-induced responses in mammalian cells have been controversial. A report of enhancement of post-replication repair by a low-dose UV-conditioning exposure (11) may also be interpreted (12) on the basis of the abnormal state of DNA replication at the time of the second exposure. Nevertheless, UV exposure of human fibroblasts has been shown to enhance levels of plasminogen activator (13) and DNA ligase (14), and agents that arrest DNA replication have been shown recently to induce synthesis of a nuclear membrane-bound protein in cell lines derived from B lymphocytes (15).Little is known about whether UV treatment actually enhances the capacity of mammalian cells to survive subsequent challenge doses of UV. Split-dose experiments are often difficult to interpret (16)...

Enhanced Reactivation and Enhanced Mutagenesis of Herpes Simplex Virus in Normal Human and Xeroderma Pigmentosum Cells

“…The higher ER ratios found with HSV by Coppey and Menenez (2) may be explained by differences in the experimental protocol or by the fact that growing cultures express higher ER levels than do resting cells (11). Our finding that contact-inhibited resting cells express these conditional responses is in agreement with results from other investigations which show that ER occurs in all stages of the cell cycle, as well as in G-1 arrested cultures (15,16,19).…”

Enhancement of Photorepair of Ultraviolet‐induced Pyrimidine Dimers by Preillumination With Fluorescent Light in the Goldfish Cell Line. The Relationship Between Survival and Yield of Pyrimidine Dimers

“…In our previous work (Yasuhira et al, 1991), survival experiments suggested that the enhance- ment of PR took 4-8 h after FL-preillumination, although it was not clear how long this enhancement continued. Therefore we first studied the timecourse of the enhancement of PR by using ESS as an endpoint.…”

“…The existence of an inducible DNA repair system in higher eukaryotes has been suggested largely from host reactivation studies, but is still controversial (Radman, 1980). Some recent works showed that pretreatment of eukaryotic cells with UV or other agents augmented some kind of repair systems in terms of the recovery of their own survival (Tyrrell, 1984;Chao and Lin-Chao, 1987). It was also reported independently that such DNA damaging agents induce the synthesis of a series of proteins (Ruby and Szostak, 1985;Kartasova et al, 1987), but it is not clear whether such proteins are involved in the DNA-repair process.…”

Increase in ultraviolet sensitivity by overexpression of calpastatin in ultraviolet-resistant UVr-1 cells derived from ultraviolet-sensitive human RSa cells

“…Defects in the latter result in increased cell death. 1 On the other hand, specific signal transduction pathways including activation of protein kinases and transcription factors are also induced by ultraviolet irradiation (UV). 2,3 Previous studies have shown that one of the earliest post-UV responses is activation of tyrosine kinases such as Src, 4 EGF-receptor, 5 insulin receptor, 6 Syk 7 and ZAP-70.…”