Polycyclic aromatic hydrocarbons induction

Conney, A.H. (1982). Induction of Microsomal-Enzymes by Foreign Chemicals and Carcinogenesis by Polycyclic Aromatic-Hydrocarbons—Clowes, G.H.A. Memorial Lecture. Cancer Research 42, 4875 917. 

Horii Y, Khim JS, Higley EB, Giesy JP, Ohura T, Kannan K (2009) Relative potencies of individual chlorinated and brominated polycyclic aromatic hydrocarbons for induction of aryl hydrocarbon receptor-mediated responses. Environ Sci Technol 43(6) 2159-2165. doi 10.102 l/es8030402... 

Chemical carcinogenesis by polycyclic aromatic hydrocarbons (PAHs) is a multi-step process in which each of the steps must occur if a neoplasm is to develop. Thus, exposure to PAHs alone is not necessarily sufficient for the induction of a tumor. Many of these factors are summarized below and are discussed in various chapters of this volume. Considered here will be those factors influencing the reactions of the metabolically activated forms of the PAHs with DNA and the ways in which adducts may be detected and characterized. 

In many mammals induction of monooxygenation by polycyclic aromatic hydrocarbons is accompanied by the formation of a hemoprotein not seen to any appreciable extent in non-induced animals. This leads to an alteration in the microsomal hemoprotein populations, a change in the metabolic activity of the microsomes and, hence, possible alterations in the toxicity of other chemicals (27, 8). 

This initial study demonstrating induction of monooxygenation and hemoprotein P-450 in the rainbow trout by polycyclic aromatic hydrocarbons, but not by phenobarbital, was extended further. 

The alteration of hemoprotein(s) P-450 subpopulations in the rat may be observed spectrally, because after treatment of rats with polycyclic aromatic hydrocarbons, the Soret maximum of the carbonmonoxyferrocytochrome complex undergoes a hypsochromic shift from 450 to 448nm (50). This blue shift was not seen with rainbow trout hepatic microsomes (29,30). However, this does not preclude the induction of novel hemoproteins P-450 since (a) the induced hemoprotein(s) maty not differ spectrally from the constitutive enzymes and (b) the induced-hemoprotein may account for only a small proportion of total hemoprotein P-450, and hence its contribution to the position of the Soret maximum of carbon monoxide-treated reduced microsomes may be negligible. The latter suggestion is supported by the work of Bend et al. with the little skate. These workers have shown that hepatic microsomes from 1, 2,3,4-dibenzanthracene treated skates did not exhibit a hypsochromic shift when compared to control microsomes, however, partially purified hemoprotein exhibited an absorbance maxima at 448 nm (51). 

Gale, R.W. Long, E.R. Schwartz, T.R. Tillitt, D.E. 2000, Evaluation of planar halogenated and polycyclic aromatic hydrocarbons in estuarine sediments using ethoxyresomfin-o-deethylase induction of H4IIE cells. Environ. Toxicol. Chem. 19 1348-1359. 

The coordinated induction of the two degradative operons is not a universal characteristic of the system. In Rbodococcus sp. strain B4, isolated from a soil sample contaminated with polycyclic aromatic hydrocarbons, salicylate does not induce the genes of the naphthalene-degradative pathway (Grund et al., 1992). 

Increased P450 synthesis requires enhanced transcription and translation. A cytoplasmic receptor (termed AhR) for polycyclic aromatic hydrocarbons (eg, benzo[a]pyrene, dioxin) has been identified, and the translocation of the inducer-receptor complex into the nucleus and subsequent activation of regulatory elements of genes have been documented. A pregnane X receptor (PXR), a member of the steroid-retinoid-thyroid hormone receptor family, has recently been shown to mediate CYP3 A induction by various chemicals (dexamethasone, rifampin) in the liver and intestinal mucosa. A similar receptor, the constitutive androstane receptor (CAR) has been identified for the phenobarbital class of inducers (Sueyoshi, 2001 Willson, 2002). 

Conney AH. Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons G. H. A. Clowes Memorial Lecture. Cancer Res 1982 42 4875-4917. 

UGT1A6 is inducible by polycyclic aromatic hydrocarbons (PAH). UGT1A6 was also induced in human hepatocytes by p-naphthoflavone and in some, but not all, hepatocyte preparations by rifampin. APAP glucuronidation appears to be increased in smokers, perhaps due to PAH-mediated induction of UGT1A6. Serotonin glucuronidation was doubled in microsomes from persons with moderate-to-heavy alcohol use (54). 

Induction of monooxygenases Polycyclic aromatic hydrocarbons (PAHs) and organochlorine compounds (OCs) Organ, population... 

Shimada, T., Sugie, A., Shindo, M., Nakajima, T., Azuma, E., Hashimoto, M., Inoue, K. (2003). Tissue-specific induction of cytochromes P4501A1 and IBl by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in engineered C57BL/6J mice of arylhydrocarbon receptor gene. Toxicol. Appl. Pharmacol. 187 1-10. 

The activity (induction or inhibition) of various CYP enzymes is influenced by a variety of factors that have been identified to date. For example, genetic polymorphisms are most significant in CYP families lA, 2A6, 2C9, 2C19, 2D6, and 2E1. Nutrition effects have been documented in families lAl, 1A2, IBl, 2A6,2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 (10, 11) smoking influences families lAl, 1A2, and 2E1 (12) alcohol influences family 2E1 (13) drugs influence families lAl, 1A2, 2A6,2B6,2C, 2D6, 3A3, and 3A4,5 and environmental xe nobio tics such as polycyclic aromatic hydrocarbons. 

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