.JPG?ad=18503&adview=true)
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Office of Research (HFT-100), National Center for Toxicological Research, Jefferson, Arkansas 72079 [M. D., P. P. F., K. F. I., R. K. K., F. F. K.]; Department of Otolaryngology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 [S. J. S.]; and Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37232 [M. V. M., F. P. G.]
Putative carcinogen-DNA adducts in human larynx tissues (n = 25) from smoker and non/ex-smoker patients were examined by 32P-postlabeling and compared with the metabolic activation capacity of larynx microsomes and cytosols from the same tissues. Hydrophobic DNA adducts were evident only in smokers, and chromatographic profiles of the adducts were similar using either the butanol extraction or nuclease P1 enhancement method, which suggested that the adducts may be derived from polycyclic aromatic hydrocarbons but not aromatic amines. Immunoblots of larynx microsomes using anti-cytochrome P450 1A1/1A2, 2C, 3A4, 2E1, and 2A6 antibodies showed intensities ranging from 1–10% of that typically observed with human liver microsomes. Enzymatic assays of larynx microsomes showed appreciable activity for benzo(a)pyrene hydroxylation (P450 1A1 and 2C) but not for 4-aminobiphenyl N-oxidation (P450 1A2), which indicated that the observed immunoreactivity was for P450 1A1; this represents the highest level of this P450 yet detected in human extrahepatic tissues. Accordingly, total DNA adduct levels in the larynx correlated strongly with levels of P450 2C, 1A1, and 3A4 but not with P450 2E1 or 2A6.
Larynx cytosols also showed appreciable aromatic amine N-acetyltransferase activity for p-aminobenzoic acid (NAT-1) but not for sulfamethazine (NAT-2); however, NAT-1 activity was not correlated with total DNA adducts, which is again consistent with the lack of aromatic amine-DNA adducts detected by 32P-postlabeling. Thus, these results suggest that the DNA adducts detected in human larynx are largely derived from metabolic activation of polycyclic aromatic hydrocarbons in cigarette smoke by P450 2C, 3A4, and/or 1A1.
1 FDA/NCTR Visiting Scientist. Permanent address: Department of Hygienic Chemistry, Tohoku University, Aobayama, Aoba-ku, Sendai 980, Japan.
2 FDA/NCTR Visiting Scientist. Permanent address: Department of Pharmacology, University of Western Australia, Nedlands 6009, Australia.
3 To whom requests for reprints should be addressed.
Received 3/23/94. Accepted 7/19/94.
This article has been cited by other articles:
|
|
 |
|
  J. Hukkanen, P. Jacob III, and N. L. Benowitz Metabolism and Disposition Kinetics of Nicotine Pharmacol. Rev., March 1, 2005; 57(1): 79 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Almahmeed, J. O. Boyle, E. G. Cohen, J. F. Carew, B. Du, N. K. Altorki, L. Kopelovich, J.-L. Fang, P. Lazarus, K. Subbaramaiah, et al. Benzo[a]pyrene phenols are more potent inducers of CYP1A1, CYP1B1 and COX-2 than benzo[a]pyrene glucuronides in cell lines derived from the human aerodigestive tract Carcinogenesis, May 1, 2004; 25(5): 793 - 799. [Full Text] [PDF]
|
|
|
|
|
|
D. H. Phillips Smoking-related DNA and protein adducts in human tissues Carcinogenesis, December 1, 2002; 23(12): 1979 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fronhoffs, T. Bruning, E. Ortiz-Pallardo, P. Brode, B. Koch, V. Harth, A. Sachinidis, H. M. Bolt, C. Herberhold, H. Vetter, et al. Real-time PCR analysis of the N-acetyltransferase NAT1 allele *3, *4, *10, *11, *14 and *17 polymorphism in squamous cell cancer of head and neck Carcinogenesis, September 1, 2001; 22(9): 1405 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Olshan, M. C. Weissler, M. A. Watson, and D. A. Bell GSTM1, GSTT1, GSTP1, CYP1A1, and NAT1 Polymorphisms, Tobacco Use, and the Risk of Head and Neck Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2000; 9(2): 185 - 191. [Abstract] [Full Text]
|
|
|
|
|
|
H. Bartsch, U. Nair, A. Risch, M. Rojas, H. Wikman, and K. Alexandrov Genetic Polymorphism of CYP Genes, Alone or in Combination, as a Risk Modifier of Tobacco-related Cancers Cancer Epidemiol. Biomarkers Prev., January 1, 2000; 9(1): 3 - 28. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Iribarren, D. R. Jacobs Jr., S. Sidney, M. D. Gross, and M. D. Eisner Cigarette Smoking, Alcohol Consumption, and Risk of ARDS* : A 15-Year Cohort Study in a Managed Care Setting Chest, January 1, 2000; 117(1): 163 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ozawa, B. Schoket, L.P. McDaniel, Y.-M. Tang, C. B. Ambrosone, S. Kostic, I. Vincze, and F. F. Kadlubar Analyses of bronchial bulky DNA adduct levels and CYP2C9, GSTP1 and NQO1 genotypes in a Hungarian study population with pulmonary diseases Carcinogenesis, June 1, 1999; 20(6): 991 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Wiencke, S. W. Thurston, K. T. Kelsey, A. Varkonyi, J. C. Wain, E. J. Mark, and D. C. Christiani Early Age at Smoking Initiation and Tobacco Carcinogen DNA Damage in the Lung J Natl Cancer Inst, April 7, 1999; 91(7): 614 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lechevrel, A. G. Casson, C. R. Wolf, L. J. Hardie, M. B. Flinterman, R. Montesano, and C. P. Wild Characterization of cytochrome P450 expression in human oesophageal mucosa Carcinogenesis, February 1, 1999; 20(2): 243 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R C. Garner, K. Dingley, and C. M Dale Molecular cancer epidemiology can predict risk BMJ, January 14, 1995; 310(6972): 124a - 124. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
