Carcinogen metabolism in human skin grafted onto athymic nude mice: a model system for the study of human skin carcinogenesis.
Human skin grafted onto athymic nude mice maintains its major histological features and may provide a useful system with which to assess the carcinogen interaction with human skin. Significant differences were observed in basal levels of cytochrome P-450 and cytochrome P-448-dependent monooxygenase activities between human grafted and nude mouse epidermis. Topical application of crude coal tar (CCT) to human skin transplanted onto nude mice resulted in 3.9 & 3.5; 3.2 & 2.9 and 1.1 & 1.2 fold increases in mouse and human epidermal aryl hydrocarbon hydroxylase (AHH), ethoxyresorufin deethylase (ERD) and ethoxycoumarin deethylase (ECD) activities, respectively. CCT applied topically to mouse skin resulted in 27.8 & 6.4; 12.8 & 3.3 and 1.7 & 2.6 fold increases in mouse and human epidermal AHH, ERD and ECD activities, respectively. Topical application of coal tar either onto human transplanted skin or to mouse skin also resulted in substantial induction of hepatic and pulmonary AHH and ERD activities. These studies indicate that human skin grafted onto nude mice preserves its metabolic capacity and offers a useful model system with which to assess the effects of polycyclic aromatic hydrocarbons and CCT on cutaneous xenobiotic metabolism in the human population.
D015660:7-Alkoxycoumarin O-Dealkylase; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D002273:Carcinogens / Q000378:metabolism*; D003033:Coal Tar; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010088:Oxidoreductases / Q000032:analysis; D010105:Oxygenases / Q000032:analysis; D011083:Polycyclic Compounds / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced*; D016038:Skin Transplantation
D002273:Carcinogens; D003580:Cytochromes; D011083:Polycyclic Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene; D003033:Coal Tar; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2