[Effect of PCBs on mouse lung tumorigenesis induced by 1-nitropyrene: a preliminary report].
We have analyzed the effect of polychlorinated biphenyls (PCB, Kanechlor-400) on 1-nitropyrene (1-NP) induced lung tumor. Male A/J mice (6 weeks old) were used for the experiment. A total of 2.5 mg/kg PCB was administered intraperitoneally (PCB group), a total of 0.38 mmol/kg 1-NP was administered intraperitoneally for 17 times (1-NP group), PCB was administered followed by i.p. injection of 1-NP (PCB + 1-NP group), and only vehicle was administered (control group). The lung lesions induced were examined 18 weeks after the final treatment with 1-NP or vehicle. In control group, no neoplastic lesion in the lung was induced. In PCB group, only one lesion with adenoma was induced. In 1-NP group, various kinds of lung neoplastic lesions including hyperplasia, adenoma and adenocarcinoma were induced. In PCB + 1-NP group, both the number and size of tumors induced were significantly more than those in 1-NP group. In addition, the number of adenocarcinoma formed was more in PCB + 1-NP group than in 1-NP group. Each lesion was microdissected to collect and analyze DNA of the targeted tissue. K-ras gene mutation was detected in part of adenoma lesions and all the carcinoma lesions. The mutation was found in either 1-NP or PCB + 1-NP group, but not in control and PCB group. The pattern of K-ras mutation was CAA to CGA in codon 61 or GGT to GAT in codon 12. There was no difference in the pattern of K-ras mutation despite of the pretreatment with PCB. Although the present data are from small sample size, it was suggested that PCB may promote (but not initiate) 1-NP induced lung tumorigenesis, and may not induce K-ras mutation directly in the experimental system.
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka.
Y
Y
Nakanishi
F
F
Bai
K
K
Takayama
X H
XH
Pei
K
K
Inoue
S
S
Osaki
M
M
Izumi
Y
Y
Takaki
N
N
Hara
H
H
Tokiwa
Y
Y
Masuda
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D000818:Animals; D002273:Carcinogens; D004785:Environmental Pollutants / Q000009:adverse effects*; D011905:Genes, ras / Q000235:genetics; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D009154:Mutation / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D011721:Pyrenes
D002273:Carcinogens; D004785:Environmental Pollutants; D011721:Pyrenes; D011078:Polychlorinated Biphenyls; C032668:1-nitropyrene