Enhanced repair of benzo(a)pyrene-induced DNA damage in human cells treated with thymidine dinucleotides

The small DNA fragment thymidine dinucleotide (pTpT) stimulates photoprotec tive responses in mammalian cells and intact skin. These responses include increased melanogenesis (tanning) and enhanced repair of DNA damage induced by ultraviolet (UV) light. Here we show that pTpT treatment of human kerat inocytes enhances their repair of DNA damaged by the chemical carcinogen be nzo(a)pyrene (BP), as determined by increased expression of a transfected B P-damaged reporter plasmid containing the chloramphenicol acetyltransferase (CAT) gene. The pTpT-enhanced repair of this BP-damaged plasmid is accompl ished at least in part through activation of the p53 tumor suppressor prote in and transcription factor, because p53-null H1299 cells showed enhanced r epair only if previously transfected with a p53-expression vector. To eluci date the mechanism of this enhanced DNA repair, we examined the expression of p21 and proliferating cell nuclear antigen (PCNA), proteins known to be regulated by p53, as well as the XPA protein, which is mutated in the inher ited repair-deficient disorder xeroderma pigmentosum (XP) group A and is ne cessary for the recognition of W-induced DNA photoproducts. The p53, PCNA a nd XPA proteins were all up-regulated within 48 h after the addition of pTp T. Taken together, these data demonstrate that pTpT-enhanced repair of DNA damaged by either UV irradiation or chemical mutagens can be achieved in hu man cells by exposure to small DNA fragments at least in part through the a ctivation of p53 and increased expression of p53-regulated genes. (C) 1999 Elsevier Science B.V. All rights reserved.