Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines

Theodore L. McLemore, Charles L. Litterst, Bruno P. Coudert, Mark Chang Hwa Liu, Walter C. Hubbard, Steven Adelberg, Maciej Czerwinski, Noreen A. McMahon, Joseph C. Eggleston, Michael R. Boyd

Research output: Contribution to journalArticle

Abstract

4-Ipomeanol (IPO) is a pulmonary-specific toxin that is metabolically activated by a cytochrome P450 pathway in lung tissue. In this study, IPO metabolism, as determined by measurement of [14C]IPO covalent binding, was evaluated in a diverse sampling of 18 established, human lung cancer cell lines as well as in normal lung tissue and primary lung carcinoma tissue obtained at the time of thoracotomy from 56 patients with lung cancer. [14C]IPO covalent binding in lung cancer cell lines ranged from 248 to 1,047 pmol of bound [14C]IPO per milligram of protein per 30 minutes (mean ± SE = 547 ± 62.2). IPO metabolism in normal lung tissue ranged from 12 to 2,007 pmol of covalently bound [14C]IPO per milligram of protein per 30 minutes (mean ± SE = 549 ± 60). In lung cancer tissue, values ranged from 0 to 2,566 pmol of covalently bound [14C]IPO per milligram of protein per 30 minutes (mean ± SE = 547 ± 60, P >.3). When patients were divided into smokers and current nonsmokers (no tobacco products smoked for >6 mo), no effects of cigarette smoking were observed for either normal lung tissue or lung tumor tissue (P >.1 in all instances). A wide range of IPO metabolic activity was observed among different histological classifications of lung cancer cell lines and of fresh lung cancer tissues. IPO metabolism was simultaneously compared in normal lung tissue and lung cancer tissue from individual patients, but no positive correlation was observed (r = .10; P >.30). The results clearly demonstrate a wide range of IPO metabolism in both normal and lung cancer cells and indicate that a wide diversity of human lung cancers possess the metabolic enzyme system(s) necessary for the bioactivation of IPO to a potentially cytotoxic intermediate. Therefore, the continued exploration for any possible therapeutic potential of IPO in patients with lung cancer appears warranted.

Original languageEnglish (US)
Pages (from-to)1420-1426
Number of pages7
JournalJournal of the National Cancer Institute
Volume82
Issue number17
StatePublished - Sep 5 1990

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Lung Cancer
Lung
Activation
Chemical activation
Cells
Tissue
Carcinoma
Lung Neoplasms
Cell Line
Line
Cell
Metabolism
Proteins
Protein
Human
4-ipomeanol
Metabolic Activation
Lung cancer
Cell line
Tobacco

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

McLemore, T. L., Litterst, C. L., Coudert, B. P., Liu, M. C. H., Hubbard, W. C., Adelberg, S., ... Boyd, M. R. (1990). Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines. Journal of the National Cancer Institute, 82(17), 1420-1426.

Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines. / McLemore, Theodore L.; Litterst, Charles L.; Coudert, Bruno P.; Liu, Mark Chang Hwa; Hubbard, Walter C.; Adelberg, Steven; Czerwinski, Maciej; McMahon, Noreen A.; Eggleston, Joseph C.; Boyd, Michael R.

In: Journal of the National Cancer Institute, Vol. 82, No. 17, 05.09.1990, p. 1420-1426.

Research output: Contribution to journalArticle

McLemore, TL, Litterst, CL, Coudert, BP, Liu, MCH, Hubbard, WC, Adelberg, S, Czerwinski, M, McMahon, NA, Eggleston, JC & Boyd, MR 1990, 'Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines', Journal of the National Cancer Institute, vol. 82, no. 17, pp. 1420-1426.
McLemore, Theodore L. ; Litterst, Charles L. ; Coudert, Bruno P. ; Liu, Mark Chang Hwa ; Hubbard, Walter C. ; Adelberg, Steven ; Czerwinski, Maciej ; McMahon, Noreen A. ; Eggleston, Joseph C. ; Boyd, Michael R. / Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines. In: Journal of the National Cancer Institute. 1990 ; Vol. 82, No. 17. pp. 1420-1426.
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abstract = "4-Ipomeanol (IPO) is a pulmonary-specific toxin that is metabolically activated by a cytochrome P450 pathway in lung tissue. In this study, IPO metabolism, as determined by measurement of [14C]IPO covalent binding, was evaluated in a diverse sampling of 18 established, human lung cancer cell lines as well as in normal lung tissue and primary lung carcinoma tissue obtained at the time of thoracotomy from 56 patients with lung cancer. [14C]IPO covalent binding in lung cancer cell lines ranged from 248 to 1,047 pmol of bound [14C]IPO per milligram of protein per 30 minutes (mean ± SE = 547 ± 62.2). IPO metabolism in normal lung tissue ranged from 12 to 2,007 pmol of covalently bound [14C]IPO per milligram of protein per 30 minutes (mean ± SE = 549 ± 60). In lung cancer tissue, values ranged from 0 to 2,566 pmol of covalently bound [14C]IPO per milligram of protein per 30 minutes (mean ± SE = 547 ± 60, P >.3). When patients were divided into smokers and current nonsmokers (no tobacco products smoked for >6 mo), no effects of cigarette smoking were observed for either normal lung tissue or lung tumor tissue (P >.1 in all instances). A wide range of IPO metabolic activity was observed among different histological classifications of lung cancer cell lines and of fresh lung cancer tissues. IPO metabolism was simultaneously compared in normal lung tissue and lung cancer tissue from individual patients, but no positive correlation was observed (r = .10; P >.30). The results clearly demonstrate a wide range of IPO metabolism in both normal and lung cancer cells and indicate that a wide diversity of human lung cancers possess the metabolic enzyme system(s) necessary for the bioactivation of IPO to a potentially cytotoxic intermediate. Therefore, the continued exploration for any possible therapeutic potential of IPO in patients with lung cancer appears warranted.",
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AU - Adelberg, Steven

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