title: Variations of cortisol hydroxylation and paracetamol metabolism in patients with bladder carcinoma.
abstract: We investigated the possibility that variations of the metabolism of xenobiotic compounds might be involved in the process of bladder carcinogenesis, by studying activation reactions (phase I) and detoxification reactions (phase II) of xenobiotic compounds in a group of patients with transitional cell carcinoma of the bladder and in a group of controls hospitalised with other diseases. As an indirect estimate of activating reactions (phase I) we measured cortisol hydroxylation, expressed as the ratio between urinary 6-beta-OH-cortisol and 17-OH-corticosteroids. Cortisol hydroxylation was not increased in the group of patients when compared with controls. The variations of phase II conjugating enzymes were followed indirectly by administering paracetamol and measuring the urinary excretion of its main metabolites over a period of 12 h. The variations in the metabolic conjugation of paracetamol were expressed as a percentage of each metabolite, or of unmodified paracetamol excreted in the urine, or as the ratio between a given metabolite and unmodified paracetamol. The data were analyzed with a logistic regression model, analysing the effects of possible confounding variables such as age, smoking, alcohol, blood nitrogen, blood creatinine, glutamic-pyruvic (SGPT), glutamic-oxalacetic transaminases (SGOT) and percent recovery of paracetamol in the urine. Statistical analysis showed that the excretion of mercapturate derivatives of paracetamol was significantly increased in the group of patients. The levels of glucuronic, sulphate and cysteine metabolites were not varied significantly. Since mercapturate derivatives are formed as a consequence of the formation of short-lived metabolites of paracetamol which react with protein, nucleic acids or glutathione, the increased excretion of mercapturic acid derivatives in cancer patients might be an indication of a higher capability of forming reactive molecular species from xenobiotic compounds. We suggest that this factor might play a role in the induction of bladder cancer.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Dolara
authors.forename: M
authors.initials: M
authors.lastname: Lodovici
authors.forename: M
authors.initials: M
authors.lastname: Salvadori
authors.forename: C
authors.initials: C
authors.lastname: Saltutti
authors.forename: A
authors.initials: A
authors.lastname: Delle Rose
authors.forename: C
authors.initials: C
authors.lastname: Selli
authors.forename: D
authors.initials: D
authors.lastname: Kriebel
mesh_terms: D000082:Acetaminophen / Q000378:metabolism* / Q000493:pharmacokinetics; D000368:Aged; D001711:Biotransformation; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D000082:Acetaminophen; D006854:Hydrocortisone