Chemoprevention of 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine-induced colon carcinogenesis by 1-O-hexyl-2,3,5-trimethylhydroquinone after initiation with 1,2-dimethylhydrazine in F344 rats.

Abstract

The aim of this study is to investigate the chemopreventive effects of the synthetic phenolic antioxidant 1-O-hexyl-2,3, 5-trimethylhydroquinone (HTHQ) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colon carcinogenesis in rats after initiation with 1,2-dimethylhydrazine (DMH) in male F344 rats. Groups of 20-22, 6-week-old male F344 rats were given four subcutaneous injections of 40 mg/kg body wt of DMH during the initial 4 weeks. They were then maintained on powdered basal diet containing 0.03% PhIP alone, PhIP together with 0.5 or 0.125% HTHQ, 0.5 or 0.125% HTHQ alone or basal diet for 32 weeks. A small number (1.1 +/- 1.1/rat) of colon tumors were induced by DMH treatment alone. After initiation with DMH, the number of colon tumors was greatly increased to 8.3 +/- 5.6 by the administration of PhIP. Additional treatment with HTHQ dose-dependently decreased the multiplicity of colon adenocarcinomas to 4.9 +/- 2.8 and 2.6 +/- 1.4 with 0.125 and 0.5%, respectively. This treatment similarly reduced atypical hyperplasias of the ventral prostate. Furthermore, HTHQ significantly reduced the multiplicity of duodenal adenocarcinomas induced by DMH + PhIP or DMH alone. Immunohistochemically, HTHQ was revealed to suppress PhIP-DNA adduct formation in the epithelial cells of the colon and prostate in a separate 2 weeks experiment. The present results clearly showed that HTHQ has chemopreventive potential for PhIP-associated colon and prostate carcinogenesis. The observed inhibition may largely be due to interference with PhIP-DNA adduct formation. In addition, HTHQ has been demonstrated to inhibit duodenal carcinogenesis in the post-initiation stage.

• Authors: Mitsuru Futakuchi, Masao Hirose, Katsumi Imaida, Satoru Takahashi, Kumiko Ogawa, Makoto Asamoto, Tokutaro Miki, Tomoyuki Shirai
• Journal: Carcinogenesis (Carcinogenesis) Vol. 23 Issue 2 Pg. 283-7 (Feb 2002) ISSN: 0143-3334 [Print] England
• PMID: 11872633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• DNA Adducts
• Hydroquinones
• Imidazoles
• 1-O-hexyl-2,3,5-trimethylhydroquinone
• 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
• 1,2-Dimethylhydrazine

Topics

• 1,2-Dimethylhydrazine (pharmacology)
• Adenocarcinoma (chemically induced, prevention & control)
• Animal Feed
• Animals
• Carcinogens
• Colonic Neoplasms (chemically induced, prevention & control)
• DNA Adducts
• Duodenal Neoplasms (chemically induced, prevention & control)
• Hydroquinones (pharmacology)
• Imidazoles
• Immunohistochemistry
• Intestinal Neoplasms (chemically induced, prevention & control)
• Male
• Pancreatic Neoplasms (chemically induced, prevention & control)
• Prostatic Neoplasms (chemically induced, prevention & control)
• Rats
• Rats, Inbred F344
• Time Factors