Influence of UVA and UVB irradiation on hepatic and cutaneous P450 isoenzymes.
The influence of UVA and UVB irradiation of the skin for 1, 2 and 4 weeks on the activities of the hepatic and cutaneous P450 isoenzymes was investigated in female Wistar rats before and after systemic administration of hexachlorobenzene (HCB), a well-known porphyrogenic agent, which additionally induces P450 1A1 and P450 1A2 isoenzymes. UVA and UVB irradiation of the skin of controls and HCB-treated animals did not influence porphyrin metabolism. In the nonporphyric rats hepatic EROD (P450 1A1) activity was induced by UVB, but the activity of ADM (P450 2B) and EMDM (P450 3A) was either minimally or not affected. In the HCB-treated (porphyric) rats UVA and UVB irradiation resulted in a significant depression of HCB-induced EROD in the liver and in the skin. In both the nonporphyric and the porphyric rats UVA and UVB irradiation had no effect on hepatic ADM activity. In the liver of the nonporphyric animals EMDM activity remained unchanged after UVA and UVB irradiation, whereas in the HCB-treated animals the activity of this enzyme was increased. Finally, after UVA and UVB irradiation cutaneous EMDM activity was increased in the controls, whereas the HCB-induced increase of this enzyme in porphyric animals was decreased. In addition long-term (28 days) UVB irradiation decreased hepatic GSH content significantly in normal and porphyric rats. These experimental findings cannot be directly extrapolated to humans; however, they suggest that exposure of human skin to UV radiation may result in alterations in the activity of cutaneous hepatic and other extracutaneous P450 isoenzymes.
Goerz
G
G
Department of Dermatology, University of Düsseldorf, Germany.
Barnstorf
W
W
Winnekendonk
G
G
Bolsen
K
K
Fritsch
C
C
Kalka
K
K
Tsambaos
D
D
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000528:radiation effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006581:Hexachlorobenzene / Q000633:toxicity; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000528:radiation effects*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011164:Porphyrias / Q000139:chemically induced / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000201:enzymology* / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D007527:Isoenzymes; D006581:Hexachlorobenzene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D005978:Glutathione