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Altered aromatic amine metabolism in epileptic patients treated with phenobarbital

Wallin, H; Skipper, P L; Tannenbaum, S R; Jensen, John P A ; Rylander, L LU and Olsen, Jørgen H (1995) In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 4(7). p.3-771
Abstract

The fate of carcinogens differs among individuals who have different activities of drug-metabolizing enzymes that are important in activating and detoxifying carcinogens. A drug that profoundly alters the metabolism of the drugs and carcinogens is the anticonvulsive agent phenobarbital. To investigate why epileptic patients appear to have a low risk of cancer of the urinary bladder, and on the basis of the observation that levels of aromatic amine-hemoglobin adducts are strongly associated with various risk factors for cancer at that site, we determined aromatic amine-hemoglobin adducts in 62 epileptic patients as a surrogate measure of the reaction of carcinogenic metabolites with DNA in target tissue. Although adducts were detected in... (More)

The fate of carcinogens differs among individuals who have different activities of drug-metabolizing enzymes that are important in activating and detoxifying carcinogens. A drug that profoundly alters the metabolism of the drugs and carcinogens is the anticonvulsive agent phenobarbital. To investigate why epileptic patients appear to have a low risk of cancer of the urinary bladder, and on the basis of the observation that levels of aromatic amine-hemoglobin adducts are strongly associated with various risk factors for cancer at that site, we determined aromatic amine-hemoglobin adducts in 62 epileptic patients as a surrogate measure of the reaction of carcinogenic metabolites with DNA in target tissue. Although adducts were detected in all subjects, the levels were proportional to daily tobacco consumption. When the subjects were stratified into groups smoking 20 g tobacco/day or more, smoking <20 g/day, and not smoking, an effect of medication was detected. Epileptic patients treated chronically with phenobarbital or primidone, which is effectively metabolized to phenobarbital, were found to have lower levels of 4-aminobiphenyl adducts than patients on the other treatment (P = 0.02; ANOVA). In nonsmokers, no effect of medication could be demonstrated above background variation; however, an increasing effect was seen with tobacco consumption with only one-half the increase in adducts per g of tobacco smoked as epileptic patients on other treatment. The difference in the increases (slopes of regression lines) was highly significant statistically. This reduction in the level of hemoglobin-aromatic amine adducts is probably due to induction of detoxification enzymes in the patients treated with phenobarbital.

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keywords
Analysis of Variance, Anticonvulsants/metabolism, Epilepsy/drug therapy, Hemoglobins/metabolism, Humans, Interviews as Topic, Phenobarbital/metabolism, Risk Factors, Smoking/adverse effects, Urinary Bladder Neoplasms/etiology
in
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
volume
4
issue
7
pages
3 pages
publisher
American Association for Cancer Research
external identifiers
  • scopus:0028845269
ISSN
1055-9965
language
English
LU publication?
yes
id
ce92f953-e12b-44f2-98e2-74853b27b230
alternative location
http://cebp.aacrjournals.org/content/4/7/771
date added to LUP
2018-08-27 13:58:55
date last changed
2018-09-18 09:23:46
@article{ce92f953-e12b-44f2-98e2-74853b27b230,
  abstract     = {<p>The fate of carcinogens differs among individuals who have different activities of drug-metabolizing enzymes that are important in activating and detoxifying carcinogens. A drug that profoundly alters the metabolism of the drugs and carcinogens is the anticonvulsive agent phenobarbital. To investigate why epileptic patients appear to have a low risk of cancer of the urinary bladder, and on the basis of the observation that levels of aromatic amine-hemoglobin adducts are strongly associated with various risk factors for cancer at that site, we determined aromatic amine-hemoglobin adducts in 62 epileptic patients as a surrogate measure of the reaction of carcinogenic metabolites with DNA in target tissue. Although adducts were detected in all subjects, the levels were proportional to daily tobacco consumption. When the subjects were stratified into groups smoking 20 g tobacco/day or more, smoking &lt;20 g/day, and not smoking, an effect of medication was detected. Epileptic patients treated chronically with phenobarbital or primidone, which is effectively metabolized to phenobarbital, were found to have lower levels of 4-aminobiphenyl adducts than patients on the other treatment (P = 0.02; ANOVA). In nonsmokers, no effect of medication could be demonstrated above background variation; however, an increasing effect was seen with tobacco consumption with only one-half the increase in adducts per g of tobacco smoked as epileptic patients on other treatment. The difference in the increases (slopes of regression lines) was highly significant statistically. This reduction in the level of hemoglobin-aromatic amine adducts is probably due to induction of detoxification enzymes in the patients treated with phenobarbital.</p>},
  author       = {Wallin, H and Skipper, P L and Tannenbaum, S R and Jensen, John P A  and Rylander, L and Olsen, Jørgen H},
  issn         = {1055-9965},
  keyword      = {Analysis of Variance,Anticonvulsants/metabolism,Epilepsy/drug therapy,Hemoglobins/metabolism,Humans,Interviews as Topic,Phenobarbital/metabolism,Risk Factors,Smoking/adverse effects,Urinary Bladder Neoplasms/etiology},
  language     = {eng},
  month        = {10},
  number       = {7},
  pages        = {3--771},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
  title        = {Altered aromatic amine metabolism in epileptic patients treated with phenobarbital},
  volume       = {4},
  year         = {1995},
}