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Evidence for tbromboxane biosynthesis in established cell lines derived from human lung adenocarcinomas. Hubbard WC, Alley MC, McLemore TL, Boyd MR. ProgramDevelop- ment Research Group, DevelopmenIal Therapeutics Program, Division of Cancer Treatment, Nalional Cancer Institute, Frederick Cancer Research Facility, Frederick, MD 21703-1013. Cancer Res 1988;48: 2674-l.

Thromboxane B, (TxB,) is the stable nonenzymatic hydrolysis product of thromboxane A,, a substance implicated in the initiation of the facilitative role of thrombocytes in the metastatic process. TxB, was isolated from protein-free culture medium of cell lines Cam-3, Cam-6, A549, and A549/Asc-1, derived from human lung adenocarcinomas. TxB, and other 20-carbon fatty acid cyclooxygenase products synthe- sized from exogenous and endogenous arachidonic acid were identified by their characteristic retention indices and fragmentation of electron- capture derivatives of unlabeled and dcuterium-labeled products durign combined capillary gas chromatography-mass spectrometry. TxB, comprised 2 to 6% of 20-carbon fatty acid cyclooxygenase products biosynthesized from endogenous arachidonic acidin calcium ionophore A23187-stimulatedCalu-6andA549/Asc-1 cellsand 16 to2S%ofthese products in Cam-3 and A549 cells. The addition of 10.’ M exogenous arachidonic acid to the cultured cells resulted in a 2- to 3-fold increase in TxB, and bisenoic prostanoid production with no significant ahera- lions in the proportion of TxB, production. Prostaglandin E, and prostaglandin F(2_), two prostanoids that can bc formed either enzy- matically or nonenzymatically from prostaglandin H,, accounted for > 75% of isolatable20-carbon fatty acidcyclooxygenaseproducts synthe- sized from endogcnous and exogenous arachidonic acid.

Experimental lung tumors following specific intrabronchial appli- cation of chrysotile asbestos. Longitudinal light and electron micro- scopic investigations in rats. Fasske E. Division of Pathology, Borsfel Research Institute. D-2061 Borstel. Respiration 1988;53: 11 l-27.

Longitudinal light and electron microscopy investigations were previously carried out on Wistar rats to study the pathogenesis of pulmonary fibrosis due to asbestos. In the present study, the genesis of pulmonary carcinomas and pleural mesotheliomas have been investi- gated by light and electron microscopy on the same model after intrabronchial instillation of chrysotile B and benz(a)pyrene, as well as a combination of the two carcinogens. A single instillation of I mg chrysotile B with a fiber length between 0.05 and 0.2 ??m in 0.1 ml tricaprylinbymeansofapolyvinylcathcterintotherightlobeofthelung of 70 anesthetized 6-week-old Wistar rats caused pulmonary carcino- mas or malignant pleural mesotheliomas in 18 animals (24%). The tumors occur at intervals between 12 and 31 months after the asbestos application. By electron microscopy, small asbestos fragments can be detected under the pleural mesothclium at the earliest I year after the intrabronchial application of chrysotile. A single combined instillation of 1 mg chrysotile and 0.5 mg benz(a)pyrene does not increase the tumor incidence. With simultaneous administration of these two substances, however, lung tumors arise very much earlier than in instillation of only one of the carcinogens. Thus, an adenocarcinoma was found in the lungs after4.5 months,andapleuralmesothelioma wasalready foundafter 7.7 months. The intrabronchial instillation of benz(a)pyrene alone causes fewer lung tumors (tumor incidence IO%, interval between 13 and 33 months).

Cytogeneticabnormalitiesin humansmallcelllungcarcinoma: Cell lines characterized for myc gene amplification. Waters JJ, Ibson JM, Twentyman PR, Bleehen NM, Rabbitts PH. De- parlmenl of Clinical Cytogenerics. Adenbrooke’slfospital, Cambridge. Cancer Genet Cytogenet 1988;30:213-23.

Nine cell lines established from various malignant tissues of patients with small cell lung carcinoma (SCLC) were examined for chromoso- ma1 abnormalities and myc gene amplification. Cytogenetic studies revealed that all cell lines were aneuploid, often with a bimodal distribution with modal concentrations in the hypodiploid and hyper- triploid range. With respect to chromosome #3, deletions of 3p were confined to six of nine SCLC ‘classic’ lines. The region of overlap of the observed 3pdeletions lies within 3~21-3~24 which is in agreement with previousassignments.Sixoftheninelines tested withc-,N-,andL-myc probes showed an increase of between ten- and 100 fold in myc gene copy number. Coamplification of two or more of these genes was not observed in any cell line. Five of the six lines with myc gene amplifi- cation had cytogenetic markers of gene amplification either in tbe form of homogenously staining regions (HSR) or double minutes (DM). Our results confirm that cytogenetically visible deletions of 3p are often present in cell lines established from patients with SCLC, and that mutually exclusive c-, L-, or N-myc gene amplification is also a common event in SCLC cell lines.

Antigenic phenotype and biological characteristics of two distinct sublines derived from a small cell lung carcinoma cell line. Watanabe H, Takahashi T, Ueda R et al. Laboratory of Chemotherapy, Aichi Cancer Center, Chikusa-ku, Nagoya 464. Cancer Res 1988;48: 2544-9.

Two sublines, SCLC-MOAI (MOAl) and SCLC-MA02 (MOA2), were established from the SCLC-MO cell line, which was originally derived from an oat cell type of small cell lung carcinoma (SCLC). SCLC-MO showed typical culture morphology of SCLC, growing as tightly packed floating aggregates, while both MOAl and MOA2 grew as a monolayer. MOA2 showed markedly shorter culture doubling time and higher colony forming efficiency than SCLC-MO and MOAI. When transplanted into nude mice, both SCLC-MO and MOAI showed intcrmcdiate cell type histology, while MOA2 showed a transitional state between the classic and the variant types, while MOAI was the variant type. In contrast, MOA2 lost the biomarker characteristic of SCLC, showing rather non-SCLC type. SCLC-MO expressed NE-150 neuroendocrine antigen, but lacked PE-35 panephitelial antigen which is generally present on SCLC. It lacked also OE-130 epithelial antigen which is generally absent from SCLC. Thus, the phenotype was NE- 15O+iPE-35/OE-130.,whichwasdifferentfrom themajorphenotypeof SCLC, NEl5O+/PE-35+/OE-130. MOAI was weakly positive for PE- 35,showing NE-150’/PE-35(.)/OE-130-, while MOA2 was positive for OE-130, but lost NE-150, i.e., NE-150/PE-35’/OE-130’, showing a non-SCLCphenotypeThusagoodconcordance wasobscrvedbetween the antigenic phcnotypc and the biological characteristics of these SCLC lines. The results altogether suggested that a part of large cell carcinoma in the tumor of the patient may be derived from SCLC. Karyotypc analysis showed that there were several marker chromo- somes including deletion of chomosome 3p shared by these three cell lines, supporting the belief that MOAI and MAO2 originated from SCLC-MO. Southern blot analysis showed the amplification of the L- myc related gene, probably rcarrangcd L-myc, in the primary SCLC tumor as well as in SCLC-MO and MOAI. Northern blot analysis

showedthe2.2-kilobasetranscripts hybridized withaL-mycprobewere observed in SCLC-MO and MOAI, but not in MOA2. In contrast, the c-myc transcript was detected only in MA02. The activity of the myc gene family may contribute to certain biological characteristics of SCLC.

Differential expression of platelet-derived growth factor and trans- forming growth factor genes in small- and non-small-cell human lung carcinoma lines. SoderdahlG,BetsholtzC.JohanssonA,NilssonK,BerghJ.Deparrmenr of Pathology, University of Uppsala, S-751 85 Uppsala. Int J Cancer 1988;41:636-41.