127

Reversibility of retinoid effect on sialyltransferase activity, sialic acid content and invasive ability of human long carcinoma cells Lcdiako N, Fazely F. Helene W. Toolan Institutefor MedicalResearch, I10 Hospital Drive, Benningfon, VT 05201. Anticancer Res 1989~9: l&9- 12.

The effect of retinoid induced suppression of in vitro invasive ability of AS49 human lung carcinoma cells on sialyltransferase activity and sialic acid content was investigated. Inhibition by retinal acetate of cell invasive potential was accompanied by a significant decrease in the enzyme activity of intact cells as well as total and cell surface neuram- inidase-releasable sialic acid contents. Moreover, reversibility of the invasion-suppressed A549 cell phenotype resulted in a return of inva- sion potential, sialyltransferase activity and surface sialic acid content to invasive cell levels. These findings suggest that membrane-bound sialic acid plays a role in invasiveness of A549 cells.

A case-cohort study of lung cancer, ionizing radiation, and tobacco smoking among males at the Hanford Site Petersen GR, GilbenES, Buchanan JA, Stevens RG. HanfordEnviron- mental Healrh Foundation, P.O. Box 100, Rlchlond, WA 99352. Health Pbys 1990;58:3-11.

Results of several epidemiological studies of workers exposed occu- pationally to low levels of radiation have been reported but have not included data on smoking. The authors conducted a case-cohort study of male workers at the Hanford Site with an objective of investigating the association between lung-cancer risk and occupational radiation exposure with appropriate adjustment for tobacco use. Eighty-six lung- cancer d’eaths for the period 1965.1980 and a stratified random sample of 445 subcobortmembers were included in the study. Tobacco-usedata were obtained from medical records collected over each subject’s period of employment. Data from this study were analyzed using methods that took into account both thecast-cohort design and changes over time in tbe quality of the tobacco-w data collected. Tobacco use was not strongly related to tbe level of radiation exposure, and adjust- mentfortobaccousedidnotgreatlymodifyresultsofanalysesassessing the association between lung-cancer risk and cumulative dose equiva- lent. With or without adjustment for tobacco use, the estimated risks per unit of cumulative dose equivalent were negative, but the 95% confi- dence intervals were wide and included values several times those estimated from populations with high levels of irradiation.

Human granaloeyte colony-stimulating factor: Biologic activities aad receptor characterization on hematopoietic cells and small cell lung cancer cell lines Avalos BR, Gasson JC, Hedvat C et al. Division of Bone Marrow Tmnsplontation, Department ofInternal Medicine, Ohio Stare Giver- sity, Columbus, OH 43210. Blood 1990;75:851-7.

Human granulocyte colony-stimulating factor (G-CSF) is a regula- tory glycopmtein that stimulates the production of neutrophilic gran- ulocytes from committed hematopoietic progenitor cells both in vitro and in viva. In this report, we show that biosynthetic (recombinant) human G-CSF enhances colony formation by normal human bone marrow and the human myeloid leukemic cell lines, HL-60 and KG-l. as well asnonhematopoietic small cell lungcancerlines. H128 and H69. G-CSF also modulates multiple differentiated functions of human neutrophils, including enhanced oxidative metabolism in response to f-

Met-Leu-Phe (f-MLP), increased antibody-dependent cell-mediated cytotoxicity (ADCC), and augmented arachidonic acid release in re- sponse to ionophore and cbemotactic agents. These effects are all maximal at a concentration of 100 to 500 pmol/L. Using lzI-labeled recombinant human G-CSF, high affinity binding sites were identified on human neutrophils, the myeloid leukemia cell lines KG-l and HL- 60, and the small cell carcinoma cell lines, H128 and H69. G-CSF receptor numbers ranged between 138 and 285 sites per cell with a kd of 77 to 140 pmo& consistent with the concentrations of G-CSF that elicit biologic responses in vitro. Decreased specific binding of ‘“I-G- CSF by human neutrophils was consistently observed in the presence of

excess unlabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF), suggesting competition or down modulation by GM- CSF of the G-CSF receptor.

Tumor necrosis factor stimulates the production of pro-urokinase from the A549 lung carcinoma cell line Dosne AM, Lutcher F, Beaupain R, Samama M. CNRS UPR-405, Lob. Immunopharmacologie Experimentale, IS, Rue de I’Ecole-de-Medt- tine, 75006 Paris. Fibrinolysis 1990:4:61-6.

The effects of TNF have been studied on the fibrinolytic activity of A549 lung carcinoma cells in an attempt to provide information on the effect of this factor on the fibrinolytic balance in the microenvironment of tumour cells. The results lead to the conclusion that TNF increases the fibrinolytic activity in the vicinity of the A549 cells. Endothelial PAI is ineffective on the urokinase plasminogen activator activity produced by these cells and this enzyme has the same properties as pro- urokinase (pro-u-PA). TNF induces a 7-fold increase in the supernatant pro-u-PA after a 24h incubation period. This effect is suppressed by cycloheximide which also renders TNF highly cytotoxic for these cells. TNF-induced pro-u-PA production at the tumor site might be important in vivo for haemorrhagic necrosis considering the leukocytic chemotac- tic activity of u-PA and also a possible proteolytic effect on the turnour neocapillaries.

Neuroendocrine alterations in node mice with a human lung carci- noma producing pro-opiomelanocortin, corticotrophin-releasing hormone and arginine vasopressin Moran0 MI, De Antueno RJ, Niedfeld G, Estivariz FE. Neuroendocri- nology Unit, Departmenr ofNeurobiology. IMBICE, Casilla de Correo 403, 19OOLa Plats. Clin Endocrinol 1990;32:349-62.

A mucoepidermoid carcinoma of the lung (ICD classification X430/ 3) resected from a patient with no clinical signs of pituitary-adrenal alterations was transplanted into 2.month-old athymic nu/nu nude mice, with the purpose of studying the effects exerted by the human tumour on the host hypothalamo-pituitary-adrenal axis. The turnour produces peptides derived from different regions of pm-opiomelano- conin (POMC: ACTH, 7.6 i 0.7; N-terminal POMC, 6.6 f 0.6; B-LPW endorphin, 7.3 f 0.7; and a-MSH, 3.8 f 0.5 pmol/g wet tissue) and the neuropeptides corticotrophin-releasing hormone and arginine vaso- pressin (CRH: 3.6 f 0.4 and AVP: 1.1 f 0.2 pmol/g wet tissue). Immunohistochemical staining of consecutwe sections of the tumour indicated that staining of tumour cells for the different peptides was not uniform and although some cells co-stained with CRH and AVP, POMC-positive cells appeared to be distinct from CRH and AVP cells. Turnour extracts were chromatographed on Sephadex G-75 and frac- tions monitored for POMC-derived peptides. A single peak with char- acteristics of a-MSH was detected. The ACTH, N-POMC, and l3-LPW endorphinradioimmunoassays(RIA)detectedapaakatlargemolecular weight, eluting at the position expected for F’OMC. These RIA systems also revealed an ACTH (l-39) peak and another peak which probably correspond to 13 kDa ACTH, a peak eluting at the position of hN- POMC(148), a l3-LPH-like peak, and a smaller sized peak which may represent a- or gamma-endorphin. The ACTH, N-POMC and O-LPW endorphin contents of anterior lobe (AL) extracts, but not neutrointer- mediate lobe (NIL) extracts, showed a striking decrease in tumour- bearing (TB) nude mice. However, while no dlfferencc was seen in the a-MSH content of AL extract between TB and control (C) nude mice, it decreased in NIL extracts of TB animals. The contents of CRH and AVP in stalk-median eminence extracts of TB nude mice was signifi- cantly lower man that 0~ L nuue mice. nasal plasma cort1costero1us were raised in TB nude mice at levels comparable to those in stressed Cnudemice,andalthoughadrenalweightsdidnotvarybetweenTBand C nude mice, morphological changes indicating hypertmphy were found in the adrenal glands of the host animals. It was concluded that the tumour dramatically alters the hypothalamo-pituitary-adrenal axis of the host, and that it may be a useful model for studying turnour-host interactions in ectopic hormone-producing turnours.