Human 8-oxoguanine-DNA glycosylase 1 protein and gene are expressed more abundantly in the superficial than basal layer of human epidermis.
Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) repairs 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) which results from oxidation of guanine. Reactive oxygen species (ROS) formed in response to ultraviolet (UV) radiation cause this DNA damage, which is involved in pathological processes such as carcinogenesis and aging. The initiation of skin tumors probably requires penetration of UV to the actively dividing basal layer of the epidermis in order for acute damage to become fixed as mutations. Previously, the majority of UVB fingerprint mutations have been found in the upper layers of human skin tumors, while UVA mutations have been found mostly in the lower layer. Our aim was to determine whether this localization of UVA-induced DNA damage is related to stratification of the repair-enzyme hOGG1. Anti-hOGG1 immunohistochemical staining of frozen sections of human foreskin, adult buttock skin, and reconstructed human skin samples showed the highest expression of hOGG1 in the superficial epidermal layer (stratum granulosum). Study of the hOGG1 mRNA expression again showed the highest level in the upper region of the epidermis. This was not regulated by UV irradiation but by the differentiation state of keratinocytes as calcium-induced differentiation increased hOGG1 gene expression. UVA-induced 8-oxo-dG was repaired more rapidly in the upper layer of human skin compared to the lower layers. Our results indicate that weaker expression of the nuclear form of hOGG1 enzyme in the basal cells of the epidermis may lead to a lack of DNA repair in these cells and therefore accumulation of UVA-induced oxidative DNA mutations.
Javeri
Arash
A
Bosch Institute, Sydney Cancer Center, Dermatology Research Laboratories, The University of Sydney, NSW 2006, Australia.
Huang
Xiao Xuan
XX
Bernerd
Françoise
F
Mason
Rebecca S
RS
Halliday
Gary M
GM
D002454:Cell Differentiation; D002478:Cells, Cultured; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D004817:Epidermis / Q000378:metabolism*; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000502:physiology; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014466:Ultraviolet Rays
D012333:RNA, Messenger; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human