Environmental chemicals enzyme induction

These phenomena exhibit very different timescales, ranging from minutes for enzyme induction and derepression to days for sufficient population growth to undetermined lengths of time for successful mutations. Thus one or more of these factors may make it difficult to predict how fast a chemical in a particular environmental setting will undergo even the initial step of biodegradation. 

Little is known of the mechanisms by which environmental chemicals deplete retinoid stores. In many field studies there is evidence of increased activity of phase I and II biotransformation enzymes, and both are thought to directly metabolize retinoids. P450 enzymes also produce oxyradicals causing oxidative stress34,72,73, which may lead to retinoid use as antioxidants. There was evidence of oxidative stress and retinoid depletion in lake trout inhabiting an area contaminated with iron-ore mine tailings80, yet it is unlikely that this exposure would be associated with induction of phase I or II biotransformation enzymes. 

The toxieity of triehloroethylene is dependent upon metabolism and induction of cytochrome P450. Triehloroethylene is metabolized through chloral hydrate to compounds including trichloroacetic acid and dichloroacetic acid which alter intercellular communication, induce peroxisome proliferation and may promote tumor production. Significant variability in trichloroethylene metabolism in 23 human haptic microsomal samples was reported by Lipscomb et al. It was also demonstrated that the trichloroethylene metabolism is dependent on enzymatic activities of the cytochrome system, and they conclude that their data indicates that humans are not uniform in their capacity for CPY dependent metabolism of trichloroethylene and increased activity may increase susceptibility to trichloroethylene induced toxicity in humans. These observations are compatible with the variability reaction which is depending on nutritional factors, enzyme induction factors, hormonal factors and interaction with other environmental chemicals, prescription medications and general health conditions, and explains the variable reports as far as trichloroethylene and level of liver toxicity in the various individuals studied. 

Elimination can be accomplished by passive diffusion when external concentrations are lower than internal concentrations favoring outward flux and by enzymatic pathways that convert hydrophobic parent compounds to more polar metabolites that can be more readily excreted by those taxa that possess a kidney or kidney-like organ (vertebrates and invertebrates such as annelids, molluscs, and arthropods). Conversion of the hydrophobic PAH to a more polar metabolite will decrease its ability to diffuse through the gill membrane, thus favoring the excretory route. The rate of elimination may be affected by environmental factors such as temperature and salinity, and by physiological factors, including reproductive state, age, sex, stress, and enzyme induction, in addition to such factors as route of uptake, chemical hydrophobicity, and exposure history. 

The initial species present, their relative concentrations, the induction of their enzymes, and their ability to acclimate once exposed to a chemical are likely to vary considerably, depending upon such environmental parameters as temperature, salinity, pH, oxygen concentration (aerobic or anaerobic), redox potential, concentration and nature of various substrates and nutrients, concentration of heavy metals (toxicity), and effects (synergistic and antagonistic) of associated microflora (Howard and Banerjee, 1984). Many of the parameters affect the biodegradation of chemicals in the environment as well as in biodegradation test systems used to simulate the environment. 

The expression level of DMEs is not a fixed immutable property of the individual. Many DMEs are highly responsive to environmental influences—for example, to modulation by endogenous regulatory signals or to induction by xenobiotic chemicals. The five P450 enzymes that typically are most abundant in human liver (CYPs 3A4, 2C9, 1A2, 2E1, and 2C19) (6,7) all are subject, to various degrees, to induction by xenobiotic chemicals as are important Phase II enzymes in the GST or UGT families. 

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