Skin tumor promotion is associated with increased Type V collagen content in the dermis

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Abstract
The effects of modification of poly(ADP-ribosyl)atlon reac tions have been examined In normal (F107) and ataxia telangieclasia (AT23) flbroblasts following damage by methyl methanesuiphonate (MMS) and u.v. light. The technique of benzoylated DEAE (BD)-cellulose chromatography was util ized to estimate both the extent and nature of the damage to DNA Induced by these agents and to examine the effects of an inhibitor of poly(ADP-ribose) synthetase, 3-aminobenz- amide (3AB), on these parameters. Single strand breakage, determined by nucleoid sedimentation, and levels of poly ADP(ribose) synthesis were monitored. Increase in the pro portion of DNA containing single-stranded regions, as m by stepwise elution from BD-cellulose, was observed follow ing MMS damage In both cell types. In the presence of 3AB, a further accumulation of DNA containing single-stranded regions occurred, with the effect being more prominent in AT23 fibroblasts. U.v. light damage did not induce increased binding to BD-cellulose in normal cells, and the increase observed in AT23 cells was much less than that seen follow ing alkylatlon damage. Examination of the nature of single- stranded damage by caffeine gradient elutlon from BD-cell ulose following MMS treatment revealed discrete structural lesions, which were enhanced in the presence of 3AB. A similar effect was exerted by arabinofuranosyl cytosine. The behaviour of these intermediates, which could be associated with repair, was not in accord with the suggestion that 3AB Inhibits only the ligation stage of the repair process. Our results suggest that specific intermediate stages in DNA repair are sensitive to 3AB, and it seems likely that these stages occur prior to ligation.