Levels Of Aryl Hydrocarbon Hydroxylase Activity Research Articles

Monocyte aryl hydrocarbon hydroxylase (AHH) activity mimics Kupffer cell and hepatocyte AHH activity in an animal model of liver disease

We have previously reported that monocyte aryl hydrocarbon hydroxylase (AHH) activity is depressed in patients with liver disease and is decreased more in cirrhosis than in early stage liver disease. To determine if monocyte AHH activity reflects liver AHH activity, we studied an animal model of cirrhosis, i.e., yellow phosphorus induced cirrhosis in the pig. AHH activity was detectable in monocytes isolated from peripheral blood of normal pigs (0.32 +/- 0.13 nmol.mg-1 P.h-1, n = 11) and was comparable to the level of AHH activity in hepatic Kupffer cells isolated from wedge or needle biopsies of livers of normal pigs (0.38 +/- 0.21, n = 7). The AHH level in pig Kupffer cells was approximately 10% of the AHH level in hepatocytes and microsomes. To induce liver disease, pigs were administered yellow phosphorus (0.6 mg/kg) 5 days per week for 16 weeks. At 4 weeks of treatment, monocyte AHH activity was not different from control and liver histology was normal. Depression of monocyte AHH activity was evident at 8 weeks of treatment when liver fibrosis was seen histologically. At 12 weeks of treatment when histology revealed extensive liver fibrosis and collagen levels were elevated, the level of monocyte AHH activity was decreased 67% compared with controls. Similar changes were observed at 12 weeks in Kupffer cell AHH activity (86% decrease) and hepatocyte AHH activity (70% decrease) compared with controls. These results suggest that monocyte AHH activity reflects liver AHH activity and may be a good indicator of change in liver enzyme function in liver disease in the pig model of cirrhosis.

The aromatic hydrocarbon receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin and variable levels of induced aryl hydrocarbon hydroxylase activity in clones of mouse hepatoma cells.

Induction of aryl hydrocarbon hydroxylase (AHH) activity was studied in clones and subclones of mouse hepatoma (Hepa-lcl) cells. When maximally induced, one clone had significantly lower (p less than 0.005), two had approximately the same, and two had significantly higher (p less than 0.005) levels of AHH activity compared with Hepa-lcl. The maximal level of induced activity, relative to the parent population, in two clones chosen for further analysis was 0.14 +/- 0.09 for clone 1 (Hs-1) and 0.94 +/- 0.28 for clone 9 (Hs-9). These relative levels were stable over a period of 10 months and were similar when activity was induced either with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or benz[a]anthracene. Subclones of Hepa-lcl cells, derived from the Hs-9 clone, also demonstrated variation in induced AHH activity. When maximally induced with TCDD, six subclones had significantly lower AHH activity (p less than 0.005), two had approximately the same, and one had significantly higher levels (p less than 0.005) compared with the progenitor Hs-9 population. Comparative analysis of Ah receptor characteristics in two unselected clones of Hepa-lcl with significantly different levels of AHH activity demonstrated that there was no apparent correlation between relative level of induced AHH activity and (i) total quantity of Ah receptor (cytosol and nuclear), (ii) receptor affinity for TCDD and number of receptor sites in each cell, (iii) subcellular distribution of [3H]TCDD, or (iv) specificity and saturable nature of binding. Coordinate measurement of the concentration of nuclear receptor and absolute induced AHH activity in Hepa-lcl and its clones had a positive correlation (r = 0.79).

Effect of steroid hormone treatment on aryl hydrocarbon hydroxylase activity in the Syrian hamster kidney

Aryl hydrocarbon hydroxylase (AHH) activity was determined in castrate and intact male Syrian hamster kidney and liver microsomes following in vivo treatment with either diethylstilbestrol (DES) or 17β-estradiol as well as other steroid hormones. After 1 month of estrogen treatment, there was a 5-fold decline in AHH activity in castrated hamster kidneys compared with untreated castrate levels. the amount of AHH activity in the kidney was depressed more than 75% of untreated castrate levels even after the estrogen had been withdrawn for 6 days. Consistent with a nearly 2.5-fold higher renal AHH activity observed in intact male hamsters compared to castrates was the finding of a 1.7-fold elevation in the activity of this enzyme after treatment of castrated animals with androgen[5α-dihydrotestrosterone (5α-DHT)] for 1 month. Moreover, following withdrawal of estrogen from intact hamsters, the increase in AHH activity in the kidney essentially paralleled the rise in serum testosterone levels. In castrated animals, the depression of AHH activity by estrogen was partially reversed by concomitant 5α-DHT treatment. However, no appreciable changes were seen in liver AHH activity with androgen treatment in the presence or absence of estrogen. Similarly, the level of AHH activity, which was nearly 7- and 14-fold higher than intact and castrate kidney levels, respectively, was not altered by estrogen treatment. Neither progesterone nor cortisone had any effect on the levels of AHH activity in either the kidney or liver. Therefore, AHH activity in the male hamster kidney, but not the liver, is responsive to both estrogens and androgenic hormone.

A twin study of aryl hydrocarbon hydroxylase (AHH) inducibility in cultured lymphocytes.

Aryl hydrocarbon hydroxylase (AHH) inducibility was studied in cultured lymphocytes from 28 monozygotic (MZ) and 19 dizygotic (DZ) twin pairs. The results indicate that the induced level of AHH activity as well as inducibility (expressed as the ratio between levels in induced and non-induced cells) are inherited. The best (h2) estimate of heritability is 0.7. There was no suggestion that non-induced AHH activity level is an inherited trait. Inducibility of AHH was not normally distributed and the distribution observed in this limited series might even be trimodal. The results of the study appear to confirm previous reports that AHH inducibility is an inherited trait, and do not exclude the possibility that the major part of the variation is controlled by one locus.

In vitro induction of aryl hydrocarbon hydroxylase in human pulmonary alveolar macrophages by benzanthracene

Aryl hydrocarbon hydroxylase (AHH) was induced in human pulmonary alveolar macrophages (PAMs) cultured in the presence of benzanthracene. Time and dose--response curves were established for in vitro induction of this enzyme system in PAMs. In addition, a positive correlation was noted between the level of AHH activity in freshly lavaged PAMs and the in vitro inducibility of the enyzme in these cells from either nonsmokers or cigarette smokers. Measurements of the inducibility of AHH in cultured human PAMs provide an experimental system suitable for studying the mechanisms responsible for the initiation of pulmonary carcinogenesis.