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- Title
Human Hair Follicle Benzo[a]pyrene and Benzo[a]pyrene 7,8-diol Metabolism: Effect of Exposure to a Coal Tar-Containing Shampoo.
- Authors
Merk, Hans F.; Mukhtar, Hasan; Kaufmann, Irene; Das, Mukul; Bickers, David R.
- Abstract
Assay systems for the evaluation of carcinogen interaction with human tissues are essential for assessing cancer risk. Hair follicles are a readily available source of human epithelial tissue and offer an excellent system with which to study carcinogen metabolism in human populations. In this study freshly plucked human hair follicles were employed to measure the metabolism of benzo[a]pyrene (BP), benzo[a]pyrene-7,8-diol (BP 7,8-diol), and the enzymemediated binding of [³H]-BP to DNA. The effect of human exposure to a curde coal tar (CCT)-containing shampoo, a preparation rich in polycyclic aromatic hydrocarbons (PAHs), on these parameters was also evaluated. Twelve healthy volunteers were studied before and after shampooing their hair daily for 4 days with the CCT-containing shampoo. Wide interindividual variation was obseved in basal cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) activity whcih ranged from 0.6-17.6 fmol water-soluble BP metabolites/h/hair follicle (mean ± SE of 32 individuals was 9.7 ± 0.9). After use of the shampoo for 4 days AHH activity increased in 10 of the 12 volunteers (150-148%) and enhancement of enzyme-mediated binding of BP to DNA was detected in most subjects. Hair follicles were shown to convert BP to several metabolic species including BP 7,8-diol, a major precursor of the ultimate carcinogenic metabolite of BP. Benzo[a]pyrene-7,8-fiol itself was also metabolized by the human hair follicles in this system. Clotrimazole, a known inhibitor of the metabolism of BP as well as the carcinogenicity of the hydrocarbon in rodent skin, was found to inhibit AHH and the in vitro metabolism of BP and BP 7,8-diol in human hair follicles.Oral administration of a similar antifungal imidazole, ketoconazole at a dose of 200 mg daily for 5 days , to healthy volunteers also resulted in >90% inhibition of hair follicle AHH activity. These studies indicate that hair follicles represent an accessible tissue suitable for assessing the extent of PAH carcinogen metabolism in human subjects. Furthermore, enzyme activity critical to cancer induction by PAHs was shown to be inducible following the use of a CCT-containing shampoo. This carcinogen-activating enzyme system was substanitally inhibited by imidazole compounds, suggesting that they may prove effective as anticarcinogens in human populations.
- Subjects
HAIR follicles; BENZOPYRENE; COAL-tar colors; SHAMPOOS; EPITHELIUM; METABOLISM; HYDROCARBONS
- Publication
Journal of Investigative Dermatology, 1987, Vol 88, Issue 1, p71
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12465053