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Modulation of apud characteristics of human lung cancer cell lines by 5-hydroxytryptophan (5HTP)
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Affinity and content of GR and AR in malignant tissues was related to differentiation. Grades II and III SCC has a lower affinity and higher content of AR than Grades III-IV. There was no difference in ADC. In contrast, GR affinity and content were higher in Grade III ADC compared to Grades I and II with no difference in SCC. Our data suggest that there is a significant incidence of specific, high affinity receptors for GR, AR and ER present in normal adult human lung and bronchogenic carcinoma cytosols, and provide an opportunity to examine the potential influence of steroids on the natural history of lung carcinoma. Xenobiotic-Metabolising Enzyme Activity in H ~ a n Non-Small Cell Derived Lung CancerlCell Lines (~SCCL). i Falzon ,IM., Wiebel , F., McMahon , J.B., Schuller , H . M . i . Laboratory of Experimental Therapeutics and Metabolism, DCT, DTP, NCI, NIH, Bethesda, MD 20205, U.S.A. 2. Institute for Toxicology and Biochemistry, Gesellschaft f6r Strahlen- und Umweltforschung, D-8042, Neuherberg, West Germany. The xenobiotic-metabolising enzyme activity in human NSCCL was studies using the two cell lines NCI-H322 (which is of Clara cell origin) and NCI-H358 (which shows features of alveolar type II cells). Both cell lines contained low but significant aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin 0-deethylase (ECOD) activities. These activities were highly inducible by ~-naphthoflavone or benzo(a) anthracene (an average 20-fold increase). Phenobarbitone and dexamethasone did not induce the native activity. In the induced cells, AHH and ECOD were inhibited by ellipticine or a-naphthoflavone. Cimetidine or metyrapone were less effective inhibitors. No aldrin epoxidase, UDPglucuronyltransferase or glutathione S-transferase activit&es were detectable in either of the induced or uninduced cell lines. NADPH-cytochrome c reductase activity was present. These results show that NCI-H322 and NCI-H358 possess cytochrome P-448 dependent monooxygenase activity and are thus capable of activating many potentially carcinogenic chemicals. They offer a useful model system to study the processes of chemical carcinogenesis in human lung, especially as such studies will not be significantly complicated by competing detoxification pathways.
A.F., Schuller I, H . M . I . Laboratory of Experimental Therapeutics and Metabolism. 2. NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20205. Amine precursor uptake and decarboxylation (APUD) are properties of cells derived from human small cell carcinoma of the lung (SCCL) Formaldehyde-induced fluorescence (FIF) of intracellular biogenic amines has thus been used for APUD cell identification. FIF is often only detected after pretreatment with amine precursors such as 5HTP. Pretreatment may induce FIF by increasing levels of 5-hydroxytryptamine (5HT) and this fluorogenic amine is thought to be stored in intracellular dense-cored granules (DCG), another hallmark of APUD cells. Two established cell lines from SCCL and a cell line derived from a human carcinoid have been used to study the effects of 5HTP on FIF, intracellular levels of 5HT and DCG. In all 3 cell lines, FIF reached a maximum 30 min after exposure and remained constant for 18 hr in the presence of 5HTP removal. Intracellular 5HT levels determined by immunoperoxidase staining with an anti-5HT antiserum paralleled FIF in the 3 cell lines, however, staining persisted 3-4 hr. The number of DCG present in the cytoplasm of each cell line was unchanged after 30 min exposure. However, after an 18 hr exposure there was a dramatic increase in the number of granules in the carcinoid-derived cell line and in one of the SCCL cell lines. These data indicate that the kinetics of FIF expression were similar in the 3 cell lines and FIF correlated with the intracellular 5HT levels. This study also demonstrates that the uptake of 5HTP and its decarboxylation to 5HT is not necessarily linked to increases in DCG in SCCL and related neoplasms.
Modualtion of Apud Characteristics of H ~ a n Lung Cancer Cell Lines by 5-Hydroxytrypto~han (5HTP).
Carcinoembyonic Antigen (CEA) in Clara Cell Carci~ noma 1 Aida , S., Kimula 2, Y., Tachi 3, H., Miura 3, H. i. University Hospital, University of Tsukuba, Ibaraki-305, Japan. 2. Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki-305, Japan. 3. Yokosuka Kyosai Hospital, Kanagawa-238, Japan. The adenocarcinoma of the lung frequently shows high level of serum CEA. Ultrastructurally, adenocarcinomas have following various cell types; i. goblet cell type, 2. bronchial surface epithelial type, 3. bronchial gland mucous cell type, 4. type II alveolar cell type, and 5. Clara cell type. In this paper we examined 40 adenocarcinomas and their subtypes were compared to immuno-histochemical findings. Among five subtypes of adenocarcinoma, the Clara cell type often showed high serum level of CEA. In process of the clinical stage, the elevation of serum CEA became prominent. The goblet cell type occasionally showed high. The other three subtypes did not show CEA elevation. Immunohistochemically the cytoplasm of the Clara cell type adenocarcinoma showed strongly positive for CEA. The cell surface and perinuclear
McMahon , J.B., del Campol, A.A., Gazdar 2,
cytoplasm of the goblet cell type were also stain-
Affinity and content of GR and AR in malignant tissues was related to differentiation. Grades II and III SCC has a lower affinity and higher content of AR than Grades III-IV. There was no difference in ADC. In contrast, GR affinity and content were higher in Grade III ADC compared to Grades I and II with no difference in SCC. Our data suggest that there is a significant incidence of specific, high affinity receptors for GR, AR and ER present in normal adult human lung and bronchogenic carcinoma cytosols, and provide an opportunity to examine the potential influence of steroids on the natural history of lung carcinoma. Xenobiotic-Metabolising Enzyme Activity in H ~ a n Non-Small Cell Derived Lung CancerlCell Lines (~SCCL). i Falzon ,IM., Wiebel , F., McMahon , J.B., Schuller , H . M . i . Laboratory of Experimental Therapeutics and Metabolism, DCT, DTP, NCI, NIH, Bethesda, MD 20205, U.S.A. 2. Institute for Toxicology and Biochemistry, Gesellschaft f6r Strahlen- und Umweltforschung, D-8042, Neuherberg, West Germany. The xenobiotic-metabolising enzyme activity in human NSCCL was studies using the two cell lines NCI-H322 (which is of Clara cell origin) and NCI-H358 (which shows features of alveolar type II cells). Both cell lines contained low but significant aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin 0-deethylase (ECOD) activities. These activities were highly inducible by ~-naphthoflavone or benzo(a) anthracene (an average 20-fold increase). Phenobarbitone and dexamethasone did not induce the native activity. In the induced cells, AHH and ECOD were inhibited by ellipticine or a-naphthoflavone. Cimetidine or metyrapone were less effective inhibitors. No aldrin epoxidase, UDPglucuronyltransferase or glutathione S-transferase activit&es were detectable in either of the induced or uninduced cell lines. NADPH-cytochrome c reductase activity was present. These results show that NCI-H322 and NCI-H358 possess cytochrome P-448 dependent monooxygenase activity and are thus capable of activating many potentially carcinogenic chemicals. They offer a useful model system to study the processes of chemical carcinogenesis in human lung, especially as such studies will not be significantly complicated by competing detoxification pathways.
A.F., Schuller I, H . M . I . Laboratory of Experimental Therapeutics and Metabolism. 2. NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20205. Amine precursor uptake and decarboxylation (APUD) are properties of cells derived from human small cell carcinoma of the lung (SCCL) Formaldehyde-induced fluorescence (FIF) of intracellular biogenic amines has thus been used for APUD cell identification. FIF is often only detected after pretreatment with amine precursors such as 5HTP. Pretreatment may induce FIF by increasing levels of 5-hydroxytryptamine (5HT) and this fluorogenic amine is thought to be stored in intracellular dense-cored granules (DCG), another hallmark of APUD cells. Two established cell lines from SCCL and a cell line derived from a human carcinoid have been used to study the effects of 5HTP on FIF, intracellular levels of 5HT and DCG. In all 3 cell lines, FIF reached a maximum 30 min after exposure and remained constant for 18 hr in the presence of 5HTP removal. Intracellular 5HT levels determined by immunoperoxidase staining with an anti-5HT antiserum paralleled FIF in the 3 cell lines, however, staining persisted 3-4 hr. The number of DCG present in the cytoplasm of each cell line was unchanged after 30 min exposure. However, after an 18 hr exposure there was a dramatic increase in the number of granules in the carcinoid-derived cell line and in one of the SCCL cell lines. These data indicate that the kinetics of FIF expression were similar in the 3 cell lines and FIF correlated with the intracellular 5HT levels. This study also demonstrates that the uptake of 5HTP and its decarboxylation to 5HT is not necessarily linked to increases in DCG in SCCL and related neoplasms.
Modualtion of Apud Characteristics of H ~ a n Lung Cancer Cell Lines by 5-Hydroxytrypto~han (5HTP).
Carcinoembyonic Antigen (CEA) in Clara Cell Carci~ noma 1 Aida , S., Kimula 2, Y., Tachi 3, H., Miura 3, H. i. University Hospital, University of Tsukuba, Ibaraki-305, Japan. 2. Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki-305, Japan. 3. Yokosuka Kyosai Hospital, Kanagawa-238, Japan. The adenocarcinoma of the lung frequently shows high level of serum CEA. Ultrastructurally, adenocarcinomas have following various cell types; i. goblet cell type, 2. bronchial surface epithelial type, 3. bronchial gland mucous cell type, 4. type II alveolar cell type, and 5. Clara cell type. In this paper we examined 40 adenocarcinomas and their subtypes were compared to immuno-histochemical findings. Among five subtypes of adenocarcinoma, the Clara cell type often showed high serum level of CEA. In process of the clinical stage, the elevation of serum CEA became prominent. The goblet cell type occasionally showed high. The other three subtypes did not show CEA elevation. Immunohistochemically the cytoplasm of the Clara cell type adenocarcinoma showed strongly positive for CEA. The cell surface and perinuclear
McMahon , J.B., del Campol, A.A., Gazdar 2,
cytoplasm of the goblet cell type were also stain-