Abstract— Cultured human cells were treated with direct sunlight under conditions which minimised the hypertonic, hyperthermic and fixative effects of solar radiation. Sunlight produced similar levels of DNA strand breaks as equitoxic 254 nm UV in two fibroblast strains and a melanoma cell line, but DNA repair synthesis and inhibition of semiconservative DNA synthesis and of DNA chain elongation were significantly less for sunlight‐exposed cells. DNA breaks induced by sunlight were removed more rapidly. Thus, the repair of solar damage differs considerably from 254 nm UV repair. Glass‐filtered sunlight (> 320 nm) was not toxic to cells and did not induce repair synthesis but gave a low level of short‐lived DNA breaks and some inhibition of DNA chain elongation; thymidine uptake was enhanced. Filtered sunlight slightly enhanced UV‐induced repair synthesis and UV toxicity; photoreactivation of UV damage was not found. Attempts to transform human fibroblasts using sunlight, with or without phorbol ester, were unsuccessful.

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Sumniar>\ In luiniaii lilirolblasts. cholesU-rol oxide induced a similar degree of chrnnuwome damage (H-(i% of inetaplia.st's) and DNA repair synthesis (8-10^ of cells with lijjlitl>-lai)i'llL'd nuclei) iw low dtwes of ultraviolet litilit (UV), but did not produLc single-stratid DN.A breaks or UiN.A diuinijic detectable hy inhibition of th\inidiiie incnrpuratiini. f^hroniosoiiie aberrations were deteeted up to S week.s iifter treatment with cholesterol oxide and VW Cined treatments had almost additixe ellect.s ini the frequency iif chrotnosonie aberrations liut mit im repair s\ntht'sis. Multiple daily doses of UV did not came more atx'rrations than a single dose, Attempts to transfiirn] two fibroblast strains from nfirinal donors and three derived from nielaiiotna patients using siiiHlc atid combined treatments of U\', cholesterol oxide and hypertherniia ( !()°) were unsiicce.ssful. IXTRODICTION.The strong circumstantial evidence for a role tjf solar-derived UV in the aetiolog\-of huniati .skin cancer (Urhacli, 1975) aticl the ability of UV to trans-(ortn cultured rodent cells (CMian and Little. 1976;DiPaolo and Donovan. 1976; Mntidal atld Ili'idelherger, 1976) enconrages attetnpts to tran.storin normal human cells by UV in vitro. Au expcrinietital model of this type wt)uld be vahtabK' for testing hypotheses coticerning the iiidttction and prevention of skin Itiiiiottrs in man. Thai snili a s\stein ha.s tiot yi't l)een reported ina\' be due to the more efficient DNA excision repair systetu it) human cells or a requirement for promoting factors sueh as chemical.s, viruses or other solar \va\elengths (Frectiiiui atid Kiit) x, 1965;Goss and Parsons. 1976; Mondal and Heidelln-rger, 1976). Alternatively, if UV should act indirectly through the in situ Formation of a chemical carcinogen, then tratisformation tnight best be eflFected b\' direct administration of the coinponnd. Gholesterol-a-oxide, for example, would appear

Tests for the presence of oncornavirus-like particles in human biopsies were made by the Spiegelman simultaneous assay for 70S RNA and RNA-dependent DNA polymerase and by detection of 600-900S particles, incorporating 3H-uridine, produced by cultured biopsy cells. Thirty-one malignant melanoma biopsies from 29 patients were studied. Using the simultaneous assay, evidence of virus-like particles was found in 15/26 (58%) of melanoma biopsies, 0/3 naevi pools, 1/4 samples of skin adjacent to melanoma, 0/3 samples of normal adult skin and 0/3 prepuces. The velocity sedimentation technique was shown to be a useful screening test for oncornaviruses in studies of two virus-producing mouse cell lines (TKL-5 and WEHI-22), and was positive with 7/9 melanoma biopsies. Overall, these results are compatible with the earlier findings of similar virus-like particles in malignant melanoma cell lines, but the exact nature of the particles remains to be defined.

Following exposure to ultraviolet irradiation (UV), two of three human fibroblast strains and one of three melanoma cell lines showed lower rates of thymine dimer excision during 24 h at 40 degrees C than at 36 degrees C. All lines had lower rates at 32 degrees C. Autoradiographic studies of three fibroblast strains and four melanoma lines incubated for four hours after irradiation revealed decreased unscheduled DNA synthesis at 42 degrees C compared with 36 degrees C. The rate of semiconservative DNA synthesis was decreased at the upper temperature in both series of experiments. All eight cell lines tested showed decreased repair at 42 degrees C, as judged by slower sedimentation and increased heterogeneity of parental DNA in alkaline sucrose gradients. Experiments using the DNA synthesis inhibitor Actinomycin D suggested that these effects were due to temperature-sensitive repair synthesis. In the two lines studied, preincubation of cells at 42 degrees C apparently increased the extent of UV damage. Although by no means conclusive, these results are consistent with the possibility that temperature-sensitive DNA repair is a contributory factor in some cases of solar carcinogenesis.