Abstract Aryl Hydrocarbon Hydroxylase Research Articles

The relationship between age and cutaneous aryl hydrocarbon hydroxylase (AHH) activity.

Aryl hydrocarbon hydroxylase (AHH), a component of the mixed-function oxygenase system, has been identified in liver and in many extrahepatic tissues, including the skin. In this study, the effect of ageing on cutaneous AHH activity in both male and female Wistar and Brown Norwegian rats of two age groups (average ages being 44 and 130 weeks) was assessed using benzo(alpha)pyrene as substrate and by measuring the formation of the fluorescent metabolite 3-hydroxybenzo(alpha)pyrene. Results show that cutaneous metabolism of polycyclic aromatic hydrocarbons does not change between young adulthood and senescence in either male or female rats. Sex-related differences did occur, however, and may be explained, partly, by the existence of different molecular forms of cyt-P450. In conclusion, age does not appear to be a major determinant of basal cutaneous AHH activity in rats.

In Vitro Induction of Aryl Hydrocarbon Hydroxylase in Baboon Pulmonary Alveolar Macrophages and Peripheral Blood Lymphocytes

Aryl hydrocarbon hydroxylase (AHH) activity was measured in cultured pulmonary alveolar macrophages (PAMs) (n = 12) and peripheral blood lymphocytes (n = 72) from unrelated baboons. It was determined that optional AHH induction was observed in PAMs when cells were cultured for 24 or 48 hours in the presence of a 15 μM concentration of the inducer, benzanthracene (BA). Maximal enzyme activity was observed in mitogen-activated lymphocytes when cells were cultured for 96 or 120 hours in the presence of 10 μM BA concentration. Additionally, there were no differences in PAM or lymphocyte AHH induction when cells were cultured in different types of culture medium (P > 0.10 in all instances, using paired, 2-tailed, Student's t-test). Similarly, no differences were observed between PAM AHH activity when human AB serum or autologous baboon serum was used in the culture medium (P > 0.30). However, slightly higher BA-induced AHH levels were noted in lymphocytes cultured in the presence of autologous baboon serum as compared with human AB serum (P < 0.02). Using optimal culture conditions for PAMs and lymphocytes from individual baboons a 6.5-fold interindividual variation in PAM and a 30-fold variation in lymphocyte BA-induced AHH levels were observed (n = 8 and 64, respectively). These studies document that AHH is measurable in cultured baboon PAMs and lymphocytes and that there is wide interindividual variation in BA-induced AHH levels. The distribution of AHH activity appears to be similar to that observed in the human population.

Genetically mediated induction of aryl hydrocarbon hydroxylase activity in human lymphoblastoid cells by polychlorinated dibenzofuran isomers and 2,3,7,8-tetrachlorodibenzo-p-dioxin

Aryl hydrocarbon hydroxylase(AHH)-inducing potency of toxic polychlorinated aromatic hydrocarbons such as polychlorinated dibenzofuran (PCDF) isomers, 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in human lymphoblastoid cell lines with different AHH inducibility for 3-methylcholanthrene (3-MC) obtained from healthy subjects. Each of the cell lines was treated with eight individual PCDF isomers, TCDD, and HCB at doses of 1.9-15 ng/ml of culture medium, 1.9-7.5 ng/ml and 95 ng/ml, respectively. Lymphoblastoid cell lines were arbitrarily classified into three groups based on their AHH inducibilities with 3-MC (2.5 microM); low (3-MC/control = I less than 3), middle (3 less than or equal to I less than 6) and high (I greater than or equal to 6). Degrees of the enzyme inducibilities of the organochlorine compounds proportionally increased with those for 3-MC. AHH inducibilities with 2,3,4,7,8-pentachlorodibenzofuran(2,3,4,7,8-PCDF), 1,2,3,4,6,7-hexachlorodibenzofuran(1,2,3,4,6,7-HCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran(1,2,3,4,7,8-HCDF) were comparable to those of TCDD at doses of 7.5 ng/ml, and about twice as high as those of 2,3,7,8-tetrachlorodibenzofuran (TCDF), at the same dose, HCB, at a dose of 95 ng/ml, did not induce enzyme activity. The experimental evidence indicated that AHH inducibility by the organochlorine compounds reflected the genetic susceptibility of the cells to the phenomenon of induction, and PCDF isomers found at relatively high concentrations in tissues of mammals exerted the highest values of AHH induction.

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.

Aryl hydrocarbon hydroxylase inducibility in lung cancer patients undergoing radiotherapy.

Aryl hydrocarbon hydroxylase (AHH) inducibility was studied in cultured lymphocytes from 21 healthy control subjects and from 15 lung cancer patients selected for radiation therapy. AHH inducibility of the patients was measured prior to, during and at the end of radiation therapy. Four of 15 patients had values comparable to the healthy controls. Cellular DNA and protein measurements of cultured lymphocytes were the same for patients and healthy controls. There was no significant difference in the percentage of lymphoblast formation and percentage of cell survival between the two groups. Radiation therapy reduces the number of lymphocytes in vivo and the amount of lymphoblast formation in vitro. AHH inducibulity is signifcantly lowered by radiation in the patients who had very high inducibility at pre-treatment level. DNA and protein contents of cultured lymphocytes did not change during radiation therapy.

Aryl hydrocarbon hydroxylase in asbestos workers.

Aryl hydrocarbon hydroxylase (AHH) activity and inducibility were studied in the lymphoblasts of 47 asbestos workers and 31 control subjects. Mean inducibility (3-methylcholanthrene [MC]-or dibenz(a,h,)anthracene [DBA]-induced divided by basal enzyme activity) was greater in the occupationally exposed subjects than in the control subjects. The estimated estimated change in mean value (+/- SE) of MC inducibility was 0.88 +/- 0.21 (P less than 0.001), and that of DBA inducibility was 1.59 +/- 0.56 (P less than 0.01). Differences in inducibility values were particularly apparent in 12 pairs of spouses, in all of whom the inducibility values of the occupationally exposed subjects exceeded those of their spouses. The differences in inducibility of AHH resulted from increases in induced activity, not from any appreciable change in basal activities. They were independent of subject age, sex, smoking status, year of first exposure to asbestos, yield of lymphoblasts, or the rate of blastogenesis as measured by the incorporation of tritiated thymidine into nucleic acid. Increased AHH inducibility may bear some relation to the greatly increased risk of bronchogenic carcinoma in asbestos workers who smoke cigarettes.