Establishment of a bioassay model for lung cancer chemoprevention initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice.

Abstract

AIMS:

In order to prevent lung cancer development in people at high risk, identification of chemopreventive agents may be important. The present study was conducted to establish a bioassay model for this purpose. In particular, the time course of 4-(methylnitrosamno)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor development was examined to determine the most appropriate shortest period to assess effects of test agents, with 8-methoxypsoralen (8-MOP) as a typical example.

METHODS:

A total of 124 mice were separated into two groups (Group A: 60 mice, Group B: 64 mice), pretreated with 100ppm 8-MOP (Group A) or basal diet (Group B) for 3 days before receiving single doses of NNK (2mg/0.1ml saline/mouse i.p.) on days 0 and 7. Subgroups of 15 mice of each group were then sacrificed after 8, 10, 12, and 16 weeks.

RESULTS:

Microscopically, the earliest time point when significant differences in data for hyperplasia, adenoma and hyperplasia and adenoma could be detected was 12 weeks. A trend was noted for 8-MOP to reduce adenomas to a greater extent than hyperplasia.

DISCUSSION:

In conclusion, the results of this study showed that the double i.p. treatment with NNK and 12 weeks duration are effective for detection of lung cancer chemoprevention in our A/J mouse lung tumorigenesis model.

• Authors: Masanao Yokohira, Hijiri Takeuchi, Kousuke Saoo, Yoko Matsuda, Keiko Yamakawa, Kyoko Hosokawa, Toshiya Kuno, Katsumi Imaida
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 60 Issue 6 Pg. 469-73 (Sep 2008) ISSN: 0940-2993 [Print] Germany
• PMID: 18639446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Carcinogens
• Nitrosamines
• 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone

Topics

• Adenoma (chemically induced, pathology, prevention & control)
• Animals
• Anticarcinogenic Agents (therapeutic use)
• Carcinogens (administration & dosage, toxicity)
• Disease Models, Animal
• Drug Screening Assays, Antitumor (methods)
• Female
• Hyperplasia (chemically induced, pathology, prevention & control)
• Injections, Intraperitoneal
• Lung Neoplasms (chemically induced, pathology, prevention & control)
• Mice
• Mice, Inbred A
• Nitrosamines (administration & dosage, toxicity)
• Time Factors