© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 13, 990-998,
July 4, 2001
© 2001 Oxford University Press
Effects of Dietary N-(4-Hydroxyphenyl)retinamide on N-Nitrosomethylbenzylamine Metabolism and Esophageal Tumorigenesis in the Fischer 344 Rat
Affiliations of authors: A. Gupta, R. Nines, K. A. Rodrigo, R. A. Aziz, P. S. Carlton, D. L. Gray, M. A. Morse, G. D. Stoner, Division of Environmental Health Sciences, The Ohio State University School of Public Health and Comprehensive Cancer Center, The Ohio State University, Columbus; V. E. Steele, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD.
Correspondence to: Gary D. Stoner, Ph.D., Division of Environmental Health Sciences, The Ohio State University School of Public Health, 1148, James Cancer Hospital and Solove Research Institute, 300 West 10th Ave., Columbus, OH 43210 (e-mail: stoner.21{at}osu.edu).
Background: 9-cis-Retinoic acid (9-cis-RA) and N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive agents against epithelial tumors in the oral cavity, breast, and prostate. We tested the inhibitory activity of these retinoids against N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus. Methods: Male Fischer 344 rats were randomly assigned to receive diets either lacking or containing 9-cis-RA or 4-HPR for 1 week before tumor initiation with NMBA and then for the duration of the study. NMBA metabolism, O6-methylguanine adduct formation, and cytochrome P450 messenger RNA (mRNA) expression in the esophagi of the rats were studied to investigate the mechanisms by which dietary 4-HPR affects tumorigenesis. All statistical tests were two-sided. Results: Dietary 4-HPR resulted in a dose-dependent and statistically significant enhancement (P<.05) of tumorigenesis in response to NMBA. In two different tumor bioassays, the mean tumor multiplicity for rats fed the highest concentration of dietary 4-HPR (0.8 g/kg diet) was increased by 5.9 tumors (95% confidence interval [CI] = 1.7 to 10.1 tumors) and 6.7 tumors (95% CI = 5.6 to 7.8 tumors) compared with the mean tumor multiplicity for rats that received the control diet lacking 4-HPR. Animals fed diets containing 9-cis-RA displayed no statistically significant increase in tumorigenesis. Compared with animals fed a diet lacking 4-HPR, animals fed 4-HPR had increased NMBA metabolism in esophageal explant cultures and had higher levels of O6-methylguanine DNA adducts and CYP2A3 mRNA in their esophagi. Conclusions: Dietary 4-HPR enhances tumorigenesis in response to NMBA in the rat esophagus by increasing tumor initiation events. Dietary 4-HPR may exert paradoxical effects at some sites, such as the aerodigestive tract, by modulating the bioactivation of carcinogens in target tissues.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. D. Gulkac, G. Akpinar, H. Ustun, and A. Ozon Kanli Effects of vitamin A on doxorubicin-induced chromosomal aberrations in bone marrow cells of rats Mutagenesis, May 1, 2004; 19(3): 231 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Wong, S. E. Murphy, M. Wang, and S. S. Hecht Comparative metabolism of N-nitrosopiperidine and N-nitrosopyrrolidine by rat liver and esophageal microsomes and cytochrome P450 2A3 Carcinogenesis, February 1, 2003; 24(2): 291 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Lippman and W. K. Hong Cancer Prevention Science and Practice Cancer Res., September 15, 2002; 62(18): 5119 - 5125. [Full Text] [PDF]
|
|