Effect of 17‐β‐estradiol and testosterone on aryl hydrocarbon hydroxylase activity in mouse tissues in vivo and in cell culture

Abstract

Initiation of skin tumors by

Expression of Aryl Hydrocarbon Hydroxylase Induction and Suppression of Tyrosine Aminotransferase Induction in Somatic-Cell Hybrids

“…The half-life of BzAnthinduced hydroxylase activity in the 3T3 parent or in several hybrids was 3-4.5 hr, whether the cells were grown in control medium alone, in the presence of cycloheximide, or in the presence of actinomycin D plus cycloheximide. All of these responses of hydroxylase activity to actinomycin D and cycloheximide and the rate of degradation of the BzAnthinduced enzyme are very similar to those described (4,22,23) for hamster-fibroblast cultures. TAT activity In marked contrast to an increased extent of hydroxylase induction by BzAnth in 15 of 16 hybrids, aminotransferase induction by dexamethasone was totally suppressed in all hybrids.…”

“…The rate of hydroxylase induction in these established cell lines is distinctly different from that found in vivo (21), or in hepatic (18), or nonhepatic (22) primary-or secondary-cell cultures, wherein hydroxylase induction by polycyclic hydrocarbons is always maximal in 24-48 hr. Hydroxylase induction in 3T3 cells or in any of the hybrids by BzAnth was completely blocked by 0.40 gM actinomycin D or 3.5 MM cycloheximide added initially; such a response is very similar to that seen with fetal-hamster secondary cultures (4,22,23) or with fetal-rat primary hepatocyte cultures (19). Actinomycin D, added to the 3T3 parent or hybrid clones 12 or 23 in which hydroxylase activity had been induced, caused a delay in the usual rate of decay of induced hydroxylase activity.…”

Polychlorinated Biphenyl Induction of Hepatocellular Carcinoma in the Sprague-Dawley Rat

“…Kimura and Baba (4) also noted a higher incidence of hepatic neoplasms in female than in male Donryo rats. Sex difference in the incidence of PCB-induced hepatocarcinogenesis may be related to sex-linked differences in enzymatic activation and deactivation of carcinogens as proposed for acetylaminofluorine hepatocarcinogenicity (19), or presence of androgens or estrogens which compete for the carcinogen for metabolism as proposed for benzopyrene (20), aflatoxin (21) or dimethylbenzanthracene (22) hepatocarcinogenicity.…”

Cutaneous Carcinogenesis: Metabolic Interaction of Chemical Carcinogens with Skin

“…Thus the cutaneous enzyme has properties similar to other extrahepatic tissues and dissimilar to liver, in which the constitutive but not the induced AHH may be stimulated by the flavone (40,194,195). Estradiol and testosterone also inhibit both the constitutive and induced enzyme in skin (116).…”

“…Enzyme activities were determined in homogenates as described by Gelboin and co-workers (60,197). 60,116,117,187,196), and human skin (4,104). Aryl hydrocarbon hydroxylase activity in homogenates of mouse skin is dependent on nicotinamide adenine dinucleotide, reduced form (NADPH) and is inhibited by carbon monoxide (197).…”