DNA damage enhances melanogenesis.

摘要: Abstract Although the ability of UV irradiation to induce pigmentation in vivo and vitro is well documented, intracellular signals that trigger this response are poorly understood. We have recently shown increasing DNA repair after enhances UV-induced melanization. Moreover, addition small fragments, particularly thymine dinucleotides (pTpT), selected mimic sequences excised during photoproducts, unirradiated pigment cells or guinea pig skin induces a indistinguishable from tanning. Here we present further evidence damage and/or increases (i) Treatment with restriction enzyme Pvu II DNA-damaging chemical agents methyl methanesulfonate (MMS) 4-nitroquinoline 1-oxide (4-NQO) produces 4- 10-fold increase melanin content Cloudman S91 murine melanoma an up 70% normal human melanocytes, (ii) irradiation, MMS, pTpT all upregulate mRNA level for tyrosinase, rate-limiting biosynthesis. (iii) MMS melanocyte-stimulating hormone (MSH) binding MSH its cell surface receptor, as has been reported irradiation. Together, these data suggest important signal Because acts exclusively on because 4-NQO, at concentrations used, primarily interact DNA, such stimulus alone appears sufficient melanogenesis. Of possible practical importance, dinucleotide mimics most, if not all, effects pigmentation, tyrosinase regulation, without requirement antecedent damage.