Polychlorinated biphenyls promote 1-nitropyrene-induced lung tumorigenesis without the induction of K-ras gene mutation in A/J mice

Yoichi Nakanishi, Feng Bai, Koji Inoue, Koichi Takayama, Xin-Hai Pei, Taishi Harada, Miiru Izumi, Kanehito Kimotsuki, Hiroshi Tokiwa, Nobuyuki Hara

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Although the effects of polychlorinated biphenyls (PCBs) on human lung carcinogenesis are suggested from the massive PCBs poisoning that occurred in Japan designated "Yusho," the detailed molecular mechanism are unknown. 1 nitropyrene (1-NP), an ubiquitous and abundant environmental pollutant, is known to be detected in lung tissues derived from patients with lung cancer in Japan, and its relation to lung carcinogenesis is also suggested. We investigated the effects of PCBs (Kanechlor-400) on l-NP-induced lung tumorigenesis in A/J mice. PCBs were administered intraperitoneally followed by ip injection of 1-NP. The lung lesions were examined 18 weeks after the final treatment. In the control group, no neoplastic lesions were induced in the lung. In the PCB group, preneoplastic lesions such as hyperplasia and adenoma were induced in 2/10 (20%) mice. In 1-NP group and in PCB + 1-NP group, lung lesions including adenocarcinoma were induced in 16/20 (80%) and 13/13 (100%) mice, respectively. Both the number and the size of tumors in PCB + 1-NP group were significantly greater than those in 1-NP group. K-ras gene mutation, CAA to CGA in codon 61 or GGT to GAT in codon 12, was found in either 1-NP group or PCB + 1-NP group but not in the PCB group. There was no difference in the pattern of K-ras mutation associated with the pretreatment with PCBs. These results suggest that PCBs promote 1-NP-induced lung tumorigenesis and may support, at least in part, the mechanism of the high incidence of lung cancer in patients with Yusho.

Original languageEnglish (US)
Pages (from-to)395-403
Number of pages9
JournalTeratogenesis Carcinogenesis and Mutagenesis
Volume21
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

1-nitropyrene
ras Genes
Polychlorinated Biphenyls
Carcinogenesis
Genes
Lung
Mutation
Codon
Lung Neoplasms
Japan

Keywords

  • Carcinogen
  • Carcinogenesis
  • Lung cancer
  • Nitroarene
  • Oncogene
  • Tumor promoter
  • Yusho

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Polychlorinated biphenyls promote 1-nitropyrene-induced lung tumorigenesis without the induction of K-ras gene mutation in A/J mice. / Nakanishi, Yoichi; Bai, Feng; Inoue, Koji; Takayama, Koichi; Pei, Xin-Hai; Harada, Taishi; Izumi, Miiru; Kimotsuki, Kanehito; Tokiwa, Hiroshi; Hara, Nobuyuki.

In: Teratogenesis Carcinogenesis and Mutagenesis, Vol. 21, No. 6, 2001, p. 395-403.

Research output: Contribution to journalArticle

Nakanishi, Yoichi ; Bai, Feng ; Inoue, Koji ; Takayama, Koichi ; Pei, Xin-Hai ; Harada, Taishi ; Izumi, Miiru ; Kimotsuki, Kanehito ; Tokiwa, Hiroshi ; Hara, Nobuyuki. / Polychlorinated biphenyls promote 1-nitropyrene-induced lung tumorigenesis without the induction of K-ras gene mutation in A/J mice. In: Teratogenesis Carcinogenesis and Mutagenesis. 2001 ; Vol. 21, No. 6. pp. 395-403.
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T1 - Polychlorinated biphenyls promote 1-nitropyrene-induced lung tumorigenesis without the induction of K-ras gene mutation in A/J mice

AU - Nakanishi, Yoichi

AU - Bai, Feng

AU - Inoue, Koji

AU - Takayama, Koichi

AU - Pei, Xin-Hai

AU - Harada, Taishi

AU - Izumi, Miiru

AU - Kimotsuki, Kanehito

AU - Tokiwa, Hiroshi

AU - Hara, Nobuyuki

PY - 2001

Y1 - 2001

N2 - Although the effects of polychlorinated biphenyls (PCBs) on human lung carcinogenesis are suggested from the massive PCBs poisoning that occurred in Japan designated "Yusho," the detailed molecular mechanism are unknown. 1 nitropyrene (1-NP), an ubiquitous and abundant environmental pollutant, is known to be detected in lung tissues derived from patients with lung cancer in Japan, and its relation to lung carcinogenesis is also suggested. We investigated the effects of PCBs (Kanechlor-400) on l-NP-induced lung tumorigenesis in A/J mice. PCBs were administered intraperitoneally followed by ip injection of 1-NP. The lung lesions were examined 18 weeks after the final treatment. In the control group, no neoplastic lesions were induced in the lung. In the PCB group, preneoplastic lesions such as hyperplasia and adenoma were induced in 2/10 (20%) mice. In 1-NP group and in PCB + 1-NP group, lung lesions including adenocarcinoma were induced in 16/20 (80%) and 13/13 (100%) mice, respectively. Both the number and the size of tumors in PCB + 1-NP group were significantly greater than those in 1-NP group. K-ras gene mutation, CAA to CGA in codon 61 or GGT to GAT in codon 12, was found in either 1-NP group or PCB + 1-NP group but not in the PCB group. There was no difference in the pattern of K-ras mutation associated with the pretreatment with PCBs. These results suggest that PCBs promote 1-NP-induced lung tumorigenesis and may support, at least in part, the mechanism of the high incidence of lung cancer in patients with Yusho.

AB - Although the effects of polychlorinated biphenyls (PCBs) on human lung carcinogenesis are suggested from the massive PCBs poisoning that occurred in Japan designated "Yusho," the detailed molecular mechanism are unknown. 1 nitropyrene (1-NP), an ubiquitous and abundant environmental pollutant, is known to be detected in lung tissues derived from patients with lung cancer in Japan, and its relation to lung carcinogenesis is also suggested. We investigated the effects of PCBs (Kanechlor-400) on l-NP-induced lung tumorigenesis in A/J mice. PCBs were administered intraperitoneally followed by ip injection of 1-NP. The lung lesions were examined 18 weeks after the final treatment. In the control group, no neoplastic lesions were induced in the lung. In the PCB group, preneoplastic lesions such as hyperplasia and adenoma were induced in 2/10 (20%) mice. In 1-NP group and in PCB + 1-NP group, lung lesions including adenocarcinoma were induced in 16/20 (80%) and 13/13 (100%) mice, respectively. Both the number and the size of tumors in PCB + 1-NP group were significantly greater than those in 1-NP group. K-ras gene mutation, CAA to CGA in codon 61 or GGT to GAT in codon 12, was found in either 1-NP group or PCB + 1-NP group but not in the PCB group. There was no difference in the pattern of K-ras mutation associated with the pretreatment with PCBs. These results suggest that PCBs promote 1-NP-induced lung tumorigenesis and may support, at least in part, the mechanism of the high incidence of lung cancer in patients with Yusho.

KW - Carcinogen

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KW - Lung cancer

KW - Nitroarene

KW - Oncogene

KW - Tumor promoter

KW - Yusho

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DO - 10.1002/tcm.1027

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