Perspectives on Cyclobutane Pyrimidine Dimers—Rise of the Dark Dimers

• Published in: Photochemistry and photobiology 2022-05, Vol.98 (3), p.609-616
• Main Authors: Lawrence, Karl P., Delinasios, George J., Premi, Sanjay, Young, Antony R., Cooke, Marcus S.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antioxidants; Biological properties; Carbonyl compounds; Carbonyls; Carcinogenesis; Carcinogens; Cyclobutane; Cyclobutane pyrimidine dimers; Dimers; DNA Damage; DNA Repair; Irradiation; Melanin; Melanins; Mice; Polymers; Pyrimidine Dimers - radiation effects; Radiation; Skin; Skin - radiation effects; Ultraviolet Rays
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.13551

ABSTRACT Some early reports demonstrate that levels of cyclobutane pyrimidine dimers (CPD) may increase after UVR exposure had ended, although these observations were treated as artifacts. More recently, it has been shown unequivocally that CPD formation does occur post‐irradiation, with maximal levels occurring after about 2–3 h. These lesions have been termed “dark CPD” (dCPD). Subsequent studies have confirmed their presence in vitro, in mouse models and in human skin in vivo. Melanin carbonyls have a role in the formation of dCPD, but they have also been observed in amelanotic systems, indicating other, unknown process(es) exist. In both cases, the formation of dCPD can be prevented by the presence of certain antioxidants. We lack data on the spectral dependence of dCPD, but it is unlikely to be the same as for incident CPD (iCPD), which are formed only during irradiation. There is evidence that iCPD and dCPD may have different repair kinetics, although this remains to be elucidated. It is also unknown whether iCPD and dCPD have different biological properties. The formation of dCPD in human skin in vivo has implications for post solar exposure photoprotection, and skin carcinogenesis, with a need for this to be investigated further. UVR exposure leads to the formation of cyclobutane pyrimidine dimers (CPD). Recently, it has been shown definitively that CPD continue to form postirradiation, with maximal levels detected after about 2–4 h. These lesions have been termed “dark CPD” (dCPD) and can be generated via chemiexcited melanin (melanin*) and possibly other as yet unidentified sensitizers. In contrast, incident CPD (iCPD) are formed rapidly (i.e., 10−12 s) only upon direct absorption of UVR during irradiation. The formation of dCPD in human skin in vivo has implications for post solar exposure photoprotection and skin carcinogenesis and therefore needs to be investigated further.