The cytochromes P-448—A unique family of enzymes involved in chemical toxicity and carcinogenesis

Ioannides, Costas; Parke, Dennis V.

doi:10.1016/0006-2952(87)90659-9

Cited by 120 publications

(29 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, feprazone administration to rats had no effect on the 0-deethylation of ethoxyresorufin, a reaction catalyzed exclusively by the P450 I isoenzymes (23,24) and this was further confirmed by immunoblots which showed no increase in the levels of P450 I apoproteins. Since the P450 I family is involved in the activation of many chemical carcinogens, and is also induced by these (25), the present findings indicate that feprazone is unlikely to display genotoxicity through this mechanism.…”

Section: Discussionmentioning

confidence: 78%

Feprazone: An inducer of the P450 II B family of proteins in the rat

Smith

Ayrton

Chown

et al. 1990

J. Biochem. Toxicol.

Self Cite

View full text Add to dashboard Cite

The ability of feprazone to induce the hepatic microsomal mixed-function oxidases was investigated in the rat, with emphasis being placed on the nature of the cytochrome P-450 family induced. Treatment with feprazone enhanced the p-hydroxylation of aniline and the dealkylations of benzphetamine and pentoxyresorufin but had no effect on the O-deethylation of ethoxyresorufin. The same treatment had no major effect on total cytochrome P-450 levels but increased the spectral interaction of metyrapone with reduced cytochrome P-450. Immunoblots employing monospecific polyclonal antibodies revealed that feprazone induces the apoprotein levels of the P450 II B, but not of the P450 I, family. It is concluded that feprazone is an inducer of the rat hepatic mixed-function oxidase system showing selectivity toward the P450 II B family.

show abstract

Section: Discussionmentioning

confidence: 78%

Feprazone: An inducer of the P450 II B family of proteins in the rat

Smith

Ayrton

Chown

et al. 1990

J. Biochem. Toxicol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The stimulatory action of pretreatment of animals with phenobarbital on N-oxide formation from the heterocycles was taken as an indication of the preponderant involvement of barbiturate-inducible P-450 isoform(s) in catalysis 8,16,148 . This type of isozyme is known to accommodate within its active site nonplanar nitrogenous compounds characterized by large depth, small area-to-depth ratio and flexibility in conformation 149 . Such a favorable geometry appears to be afforded by some 9-substituted adenines.…”

Section: Enzymology Of N-oxide Formationmentioning

confidence: 99%

N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification

Hlavica

Lehnerer

2009

Patai's Chemistry of Functional Groups

View full text Add to dashboard Cite

Introduction Chemical Aspects of the N ‐Oxygenation of the C  N Functionality Occurrence of N ‐Oxygenated C  N Functionalities in Natural and Synthetic Compounds and Biological Activity Metabolic in Vivo and in Vitro Formation of N ‐Oxygenated C  N Functionalities Enzymology of the Formation of N ‐Oxygenated C  N Functionalities Further Transformations of N ‐Oxygenated C  N Functionalities Conclusions

show abstract

“…When the crude mortality percentages at 1 and 2 years were calculated in relation to AHH and EH activity, subdivided into quarters of the distribution, higher mortality was related to higher enzyme activities ( Enzyme induction by smoke constituents would be expected to increase the formation of both reactive and inactive metabolites in smokers' lung. However, it has been suggested that CYPlA-mediated insertion of oxygen into conformationally hindered positions in planar substrates, such as polycyclic aromatic hydrocarbons and aromatic amines, results in the formation of reactive intermediates which are poor substrates for subsequent conjugation and detoxication (29). In contrast, oxygenation at conformationally unhindered positions of chemicals by other cytochromes (e.g., CYP2B) is followed by rapid conjugation that results in detoxication.…”

Section: Prognostic Value Of Pulmonary Ahh and Eh Activities In Patiementioning

confidence: 99%

Carcinogen Metabolism in Human Lung Tissues and the Effect of Tobacco Smoking: Results from a Case-Control Multicenter Study on Lung Cancer Patients

Bartsch¹,

Petruzzelli²,

Flora³

et al. 1992

Environmental Health Perspectives

View full text Add to dashboard Cite

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYPIA-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or nonneoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and ph;e-Ceipoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glugtathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; -some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; I) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.

show abstract

The cytochromes P-448—A unique family of enzymes involved in chemical toxicity and carcinogenesis

Cited by 120 publications

References 92 publications

Feprazone: An inducer of the P450 II B family of proteins in the rat

Feprazone: An inducer of the P450 II B family of proteins in the rat

N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification

Carcinogen Metabolism in Human Lung Tissues and the Effect of Tobacco Smoking: Results from a Case-Control Multicenter Study on Lung Cancer Patients

Contact Info

Product

Resources

About