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


CONCLUSIONS
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.
Yokohira
Masanao
M
Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Takeuchi
Hijiri
H
Saoo
Kousuke
K
Matsuda
Yoko
Y
Yamakawa
Keiko
K
Hosokawa
Kyoko
K
Kuno
Toshiya
T
Imaida
Katsumi
K
D000236:Adenoma / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008805:Mice, Inbred A; D009602:Nitrosamines / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone