Age-related changes in benzo(a)pyrene metabolism and epoxide-metabolizing enzyme activities in rat skin

The postnatal development of microsomal aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECD), epoxide hydrolase (EH) [benzo(a)pyrene (BP)-4,5-oxide as substrate], and cytosolic glutathione S-transferase (GST) was studied in skin of Sprague-Dawley rats. Animals were treated with skin application of 3-methylcholanthrene (MCA) (40 mg/kg, 24 hr before sacrifice) or acetone. Enzyme activities were detected in animals of all ages. AHH and ECD in control rats showed slight age-dependent variation. Age-dependent differences in inducibility of skin AHH and ECD by topically applied MCA were observed. At 4, 6, 10, 18, 24, 32, and 55 days of age, the inducibility of AHH was 11, 18, 18, 19, 20, 23, and 21-fold, respectively. A similar pattern was observed for ECD. EH activity in 24-day-old skin was twice that in 4-day-old animals. GST activity remained constant throughout maturation. EH and GST activities were not altered by MCA. BP metabolism was studied in control and MCA-induced neonatal (4-day-old), young (18-day-old), and adult (55-day-old) animals. MCA treatment increased the rate of metabolism of BP at all ages studied. Higher rates of BP metabolism occurred in adult skin as compared to younger or neonatal rat skin. Inducibility of trans-7,8-diol formation by topically applied MCA was highest in the adult (19-fold) rat skin as compared to younger (12-fold) or neonatal rat skin (10-fold). These studies suggest that xenobiotic metabolism in skin of rats undergoes variable changes during aging which could exert some influence on pharmacologic responses to topically applied agents in cutaneous tissue.