Xenobiotic-metabolizing enzyme activity in human non-small-cell derived lung cancer cell lines

Miriam Falzon, James B. McMahin, Hildegard M. Schuller

Research output: Contribution to journalArticle

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Abstract

Human lung cancer cell lines in culture were investigated for the expression of monooxygenase and other xenobiotic-metabolizing enzyme activities. Two brochiolo-alveolar carcinoma derived cell lines (NCI-H322 and NCI-H358) and two small-cell carcinoma derived cell lines (NCI-H128 and NCI-H69) were used. Previous work has shown that NCI-H322 has ultrastructural features of Clara cells while NCI-H358 shows characteristics of alveolar type II cells [Schuller et al., Proc. Am. Ass. Cancer Res. 26, 27 (1985)]. NCI-H128 and NCI-H69 show very poor differentiation of cytoplasmic organelles. Cytochrome P-450 levels were spectroscopically detectable only in NCI-H322. Both NCI-H322 and NCI-H358, but not NCI-H69 and NCI-H128, exhibited aryl hydrocarbon hydroxylase (using benzo[a] pyrene as substrate) and ethoxycoumarin O-deethylase activities. These activities were highly inducible following pretreatment with the polycyclic aromatic hydrocarbons (PAH) β-naphthoflavone or benzo[a] anthracene. The PAH produced a 2-fold increase in spectroscopically detectable cytochrome P-450 levels in NCI-H322. Following induction, cytochrome P-450 was also spectroscopically detectable in NCI-H358. No aldrin epoxidase activity was present in either untreated or pretreated cell lines. Pretreatment with phenobarbitone or dexamethasone did not induce the aryl hydrocarbon hydroxylase activity in either NCI-H322 or NCI-H358. The ethoxycoumarin O-deethylase activity in β-naphthoflavone-pretreated NCI-H322 and NCI-H358 was inhibited in a concentration-dependent manner by ellipticine, α-naphthoflavone, cimetidine or metyrapone. Untreated NCI-H322 and NCI-H358 also contained cytochrome b5, NADPH cytochrome c reductase and epoxide hydrolase activities. None of these enzyme activities measured was detectable in the untreated or pretreated small-cell derived cancer cell lines (NCI-H128 and NCI-H69). These data show that the two bronchio-alveolar carcinoma derived cell lines (NCI-H322 and NCI-H358) exhibit cytochrome P-448-dependent monooxygenase activity and may thus prove useful to study the processes of xenobiotic activation in human lung.

Original languageEnglish (US)
Pages (from-to)563-568
Number of pages6
JournalBiochemical Pharmacology
Volume35
Issue number4
DOIs
StatePublished - Feb 15 1986
Externally publishedYes

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Enzyme activity
Xenobiotics
Human Activities
Non-Small Cell Lung Carcinoma
Cells
Aryl Hydrocarbon Hydroxylases
Cell Line
Enzymes
7-Alkoxycoumarin O-Dealkylase
Cytochrome P-450 Enzyme System
Bronchiolo-Alveolar Adenocarcinoma
Polycyclic Aromatic Hydrocarbons
ellipticine
Mixed Function Oxygenases
Alveolar Epithelial Cells
Metyrapone
Epoxide Hydrolases
Cytochromes b5
NADPH-Ferrihemoprotein Reductase
Small Cell Carcinoma

ASJC Scopus subject areas

  • Pharmacology

Cite this

Xenobiotic-metabolizing enzyme activity in human non-small-cell derived lung cancer cell lines. / Falzon, Miriam; McMahin, James B.; Schuller, Hildegard M.

In: Biochemical Pharmacology, Vol. 35, No. 4, 15.02.1986, p. 563-568.

Research output: Contribution to journalArticle

Falzon, Miriam ; McMahin, James B. ; Schuller, Hildegard M. / Xenobiotic-metabolizing enzyme activity in human non-small-cell derived lung cancer cell lines. In: Biochemical Pharmacology. 1986 ; Vol. 35, No. 4. pp. 563-568.
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