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Sister-chromatid exchanges in human bronchial epithelial cells
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The ERBAB gene codes for a DNA-binding thyroid hormone receptor (THR) and maps to chromosome 3p21-~25, overlapping a 3p deletion characterizing small-cell lungcarcinoma(SCLC).ADNAclonedetecting an RFLP at the ERBAD locus has been used to probe a large number of lung tumors. Virtually all SCLC had lost heterozygosity, showing that the 3p deletion in SCLC includes this gene. A substantial but smaller proportion of non-small-cell carcinomas had lost hetemzygosity at ERBAB. Among all non-small-cell tumors some had lost hetemzygosity attheproximallocusDFNl5S2(band3p21)butnotatERBAO,whereas none were found where the reverse was true. Therefore, the locus which plays a role in non-small-cell tumorigenesis probably lies closer to DNFl5S2 than to ERBAD and is almost certainly not the latter. Inhibition of experimental metastasis of murine fibrosarcoma cells by oligopeptide analogoes to the fibronectin cell-binding site. Bretti S, Neri P, Lozzi L et al. Deporrmenl of Generics, Biology and Chemisny. UniversifyofTurin, 10126 Turin. Int J Cancer 1989:43:1026. We have analyzed the effect of the synthetic oligopeptides Gly-ArgGly-Asp-Ser-Pro (GRSDSP) and Gly-Arg-Gly-Glu-Ser-Pro (GRGESP), analogues to the Iibronectin cell-binding sequence, on the formation of experimental lung metastasis. SR-BALB were injected alone or in conjunction with GRGDSP or GRGESP in the tail vein of BALB/c mice. Co-injection with GRGESP reduced by approximately 70% the number of me&static colonies per mouse. However, coinjection with the closely related peptide GRGDSP, containing the conservative substitution Glu/Asp, did not affect metastatic behavior. GRGESPpeptide anti-metastatic activity was not due to a toxic effect on tumor cells or on mice. In vitro adhesion assays testing for possible effect of the peptide on cell-matrix interactions indicated that the GRGESP peptide did not affect cell adhesion to the matrix proteins tested.
In vitro transformation of Chinese hamster lung cell line. Shibasaki Y, Ronne M. Institure of Anatomy and Cytology, Odense University. DK-5230 Odense M. Anticancer Res 1988;8: 1285-9. Karyotypical changes in connection with spontaneous in vitro transformation of primary Chinese hamster lung cultures were followed. At the 26th passage the cultures were spontaneously transformed to an established cell line in the neardiploid range (CHAL-cells). The only chromosomalchangewhichcouldbeobservedinthestemlineofCHALcultures after R-banding and karyotyping was the presence of an extra chromosome giving the following karyotype, 23,XY,+mar. The distal part of the marker showed banding patterns corresponding to 3q21-3 qter.
Inhibition by retinoids of in vitro invasive ability of human long carcinoma cells. Fazely F, Ledinko N, Smith DJ. Deparrment of Biology, Universiry of Akron, Akron, ON 44325. Anticancer Res 1988;8:1387-91. The effect of retinoid treatment of A549 human lung carcinoma cells on in vitro cell invasion using the human amnion basement membrane (BM) was investigated. A 2-&y retinoid pretreatment of the cells resulted in a significant reduction in their invasive ability. The most effective retinoid, retinol acetate, inhibited cell migration through the BM and degradation of [‘wpmline labeled BM components by 50% at noncytotoxic concentrations of 0.09, and 3 *g/ml, respectively. Inhibition by retinol acetate of A549 cell invasive potential was accompanied by a significant decrease in type IV collagenase activity and no change in transglutaminase activity. Radon daughter dosimetry in the rat tracheobronchial tree. Harley NH. New York University School of Medicine, New York, NY 10016. Radiat Pmt Dosim 1988;24:457-61. Detailed alphadosimetry for radon daughters deposited in the rat lung has been carried out. The dose calculations include the atmospheric exposure characteristics for existing animal experiments conducted at Battelle in the US and CEA in France. The alpha dose per WLMis close to that in the human tracheobronchial tree and so it is not surprising that
if bronchial epithelium in humans and rats behaves similarly for carcinogenesis that the observed lung cancer response is similar.
Radon inhalation studies in animals. Cross IT. Pacific Northwest Laboratory, Richland, WA 99352. Radiat Prot Dosim 1988;24:463-6. A summary of updated biological effects data resulting from chronic radon inhalation exposures of animals is presented. Emphasis is placed on thecarcinogeniceffectsof radonandradondecayproducts,including the influences of radon progeny exposure rate, unattached fraction and disequilibrium, and co-exposures to other pollutants. Plausible values are provided for the radon (radon progeny) lifetime lung cancer risk coefficients. Sister-chromatid exchanges in human bronchial epithelial cells. Hsu I-C, Galati A, Stoner GD. Deparment ofParhology, University of Maryland School of Medicine, Eal~imore, MD 31301. Toxic01 Vitro 1989;3:21-5. One method of assessing the genotoxic effects of exposure to environmental agents is by determining the frequency of sister chromatid exchanges in exposed cells. In the present study, a procedure for observing sister chromatid exchanges in adult human bronchial epithelial cells exposed to a carcinogen has been developed. Using this procedure, the frequencies of sister chromatid exchanges in untreated cells from two individuals were found to be 5.1 * 1.8 and 6.5 * 1.4 per metaphase (mean * SD). Cells from the first individual exposed to 7,12dimethylbenz[a]anthraceneat 0.5,l and2*g/ml had7.8 *2.2,13.3.1, 18.7.3.7sisterchromatidexchangespermetaphase,respectively.This method is likely to be particularly useful for observing sister chromatid exchanges in cellsthat havearelatively slowgrowthratein the presence of bromodeoxyuridine and for which preparation of a large number of metaphasechromosomesisdifficult.Inaddition,theprocedureprovides a means of assessing genotoxic effects in the lung by examining the direct effects of pollutants on the chromosomes of the target cells for human lung cancer. Generation andexpansion of lymphokine-activated killer cellsfrom lymph node lymphocytes in human lung cancer. Yano T, Yasumoto K, Nomom K. Departmenl ofImmunology. Medical Imitwe of Bioregulation, Kyushu University, Higashi-ku, Fukuokn 812. Eur J Cancer Clin Oncol 1989:25:201-S.
We cultured lymph node lymphocytes (LNL) from lung cancer patients in the presenceofrecombinant interleukin 2 (rIL2). Theability of LNL to respond to rIL2 was not affected by the advance of cancer stage when tested for proliferation and for lymphokine-activated killer (LAK) activity. The LAK activity of LNL wascomparableto thatof the corresponding peripheral blood lymphocytes. The rIL2-induced proliferation of macrophage-depleted LNL was augmented by the reconstitution with autologous alveolar macrophages while the LAK activity was not affected. However, macrophage-reconstituted LNL expanded rapidlyandreached highercelldensitiesandexhibitedasignificantlylower LAK activity than macrophage-depleted LNL. The diminished LAK activity in macrophage-reconstituted LNL were markedly augmented by the subculture at a low cell density. From these results, we conclude that LNL can bc a good material for a postoperative LAK therapy and that macrophage is useful in culture of LAK cells. Evidence for prostanoid biosynthesis as a biochemical feature of certain subclasses of non-small cell carcinomas of the lung as determined in established cell lines derived from human long tumors. Hubbard WC, Alley MC, Gray GN, Green KC, McL.emore TL, Boyd MR. ProgramDevelopmen~ResearchGroup,DivisionofConcerTreatment, National Cancer Instime, Frederick Cancer Research Faciliry, Frederick, IUD 21701-1013. Cancer Res 1989;49:826-32.
Detectable levels C 0.2 pmol/106 cells) of one or more prostanoid species resultant to calcium ionophore A23187-induced biosynthesis from endogenous arachidonic acid were distributed in 28 cell lines derived from different histological classes of lung tumors as follows:
The ERBAB gene codes for a DNA-binding thyroid hormone receptor (THR) and maps to chromosome 3p21-~25, overlapping a 3p deletion characterizing small-cell lungcarcinoma(SCLC).ADNAclonedetecting an RFLP at the ERBAD locus has been used to probe a large number of lung tumors. Virtually all SCLC had lost heterozygosity, showing that the 3p deletion in SCLC includes this gene. A substantial but smaller proportion of non-small-cell carcinomas had lost hetemzygosity at ERBAB. Among all non-small-cell tumors some had lost hetemzygosity attheproximallocusDFNl5S2(band3p21)butnotatERBAO,whereas none were found where the reverse was true. Therefore, the locus which plays a role in non-small-cell tumorigenesis probably lies closer to DNFl5S2 than to ERBAD and is almost certainly not the latter. Inhibition of experimental metastasis of murine fibrosarcoma cells by oligopeptide analogoes to the fibronectin cell-binding site. Bretti S, Neri P, Lozzi L et al. Deporrmenl of Generics, Biology and Chemisny. UniversifyofTurin, 10126 Turin. Int J Cancer 1989:43:1026. We have analyzed the effect of the synthetic oligopeptides Gly-ArgGly-Asp-Ser-Pro (GRSDSP) and Gly-Arg-Gly-Glu-Ser-Pro (GRGESP), analogues to the Iibronectin cell-binding sequence, on the formation of experimental lung metastasis. SR-BALB were injected alone or in conjunction with GRGDSP or GRGESP in the tail vein of BALB/c mice. Co-injection with GRGESP reduced by approximately 70% the number of me&static colonies per mouse. However, coinjection with the closely related peptide GRGDSP, containing the conservative substitution Glu/Asp, did not affect metastatic behavior. GRGESPpeptide anti-metastatic activity was not due to a toxic effect on tumor cells or on mice. In vitro adhesion assays testing for possible effect of the peptide on cell-matrix interactions indicated that the GRGESP peptide did not affect cell adhesion to the matrix proteins tested.
In vitro transformation of Chinese hamster lung cell line. Shibasaki Y, Ronne M. Institure of Anatomy and Cytology, Odense University. DK-5230 Odense M. Anticancer Res 1988;8: 1285-9. Karyotypical changes in connection with spontaneous in vitro transformation of primary Chinese hamster lung cultures were followed. At the 26th passage the cultures were spontaneously transformed to an established cell line in the neardiploid range (CHAL-cells). The only chromosomalchangewhichcouldbeobservedinthestemlineofCHALcultures after R-banding and karyotyping was the presence of an extra chromosome giving the following karyotype, 23,XY,+mar. The distal part of the marker showed banding patterns corresponding to 3q21-3 qter.
Inhibition by retinoids of in vitro invasive ability of human long carcinoma cells. Fazely F, Ledinko N, Smith DJ. Deparrment of Biology, Universiry of Akron, Akron, ON 44325. Anticancer Res 1988;8:1387-91. The effect of retinoid treatment of A549 human lung carcinoma cells on in vitro cell invasion using the human amnion basement membrane (BM) was investigated. A 2-&y retinoid pretreatment of the cells resulted in a significant reduction in their invasive ability. The most effective retinoid, retinol acetate, inhibited cell migration through the BM and degradation of [‘wpmline labeled BM components by 50% at noncytotoxic concentrations of 0.09, and 3 *g/ml, respectively. Inhibition by retinol acetate of A549 cell invasive potential was accompanied by a significant decrease in type IV collagenase activity and no change in transglutaminase activity. Radon daughter dosimetry in the rat tracheobronchial tree. Harley NH. New York University School of Medicine, New York, NY 10016. Radiat Pmt Dosim 1988;24:457-61. Detailed alphadosimetry for radon daughters deposited in the rat lung has been carried out. The dose calculations include the atmospheric exposure characteristics for existing animal experiments conducted at Battelle in the US and CEA in France. The alpha dose per WLMis close to that in the human tracheobronchial tree and so it is not surprising that
if bronchial epithelium in humans and rats behaves similarly for carcinogenesis that the observed lung cancer response is similar.
Radon inhalation studies in animals. Cross IT. Pacific Northwest Laboratory, Richland, WA 99352. Radiat Prot Dosim 1988;24:463-6. A summary of updated biological effects data resulting from chronic radon inhalation exposures of animals is presented. Emphasis is placed on thecarcinogeniceffectsof radonandradondecayproducts,including the influences of radon progeny exposure rate, unattached fraction and disequilibrium, and co-exposures to other pollutants. Plausible values are provided for the radon (radon progeny) lifetime lung cancer risk coefficients. Sister-chromatid exchanges in human bronchial epithelial cells. Hsu I-C, Galati A, Stoner GD. Deparment ofParhology, University of Maryland School of Medicine, Eal~imore, MD 31301. Toxic01 Vitro 1989;3:21-5. One method of assessing the genotoxic effects of exposure to environmental agents is by determining the frequency of sister chromatid exchanges in exposed cells. In the present study, a procedure for observing sister chromatid exchanges in adult human bronchial epithelial cells exposed to a carcinogen has been developed. Using this procedure, the frequencies of sister chromatid exchanges in untreated cells from two individuals were found to be 5.1 * 1.8 and 6.5 * 1.4 per metaphase (mean * SD). Cells from the first individual exposed to 7,12dimethylbenz[a]anthraceneat 0.5,l and2*g/ml had7.8 *2.2,13.3.1, 18.7.3.7sisterchromatidexchangespermetaphase,respectively.This method is likely to be particularly useful for observing sister chromatid exchanges in cellsthat havearelatively slowgrowthratein the presence of bromodeoxyuridine and for which preparation of a large number of metaphasechromosomesisdifficult.Inaddition,theprocedureprovides a means of assessing genotoxic effects in the lung by examining the direct effects of pollutants on the chromosomes of the target cells for human lung cancer. Generation andexpansion of lymphokine-activated killer cellsfrom lymph node lymphocytes in human lung cancer. Yano T, Yasumoto K, Nomom K. Departmenl ofImmunology. Medical Imitwe of Bioregulation, Kyushu University, Higashi-ku, Fukuokn 812. Eur J Cancer Clin Oncol 1989:25:201-S.
We cultured lymph node lymphocytes (LNL) from lung cancer patients in the presenceofrecombinant interleukin 2 (rIL2). Theability of LNL to respond to rIL2 was not affected by the advance of cancer stage when tested for proliferation and for lymphokine-activated killer (LAK) activity. The LAK activity of LNL wascomparableto thatof the corresponding peripheral blood lymphocytes. The rIL2-induced proliferation of macrophage-depleted LNL was augmented by the reconstitution with autologous alveolar macrophages while the LAK activity was not affected. However, macrophage-reconstituted LNL expanded rapidlyandreached highercelldensitiesandexhibitedasignificantlylower LAK activity than macrophage-depleted LNL. The diminished LAK activity in macrophage-reconstituted LNL were markedly augmented by the subculture at a low cell density. From these results, we conclude that LNL can bc a good material for a postoperative LAK therapy and that macrophage is useful in culture of LAK cells. Evidence for prostanoid biosynthesis as a biochemical feature of certain subclasses of non-small cell carcinomas of the lung as determined in established cell lines derived from human long tumors. Hubbard WC, Alley MC, Gray GN, Green KC, McL.emore TL, Boyd MR. ProgramDevelopmen~ResearchGroup,DivisionofConcerTreatment, National Cancer Instime, Frederick Cancer Research Faciliry, Frederick, IUD 21701-1013. Cancer Res 1989;49:826-32.
Detectable levels C 0.2 pmol/106 cells) of one or more prostanoid species resultant to calcium ionophore A23187-induced biosynthesis from endogenous arachidonic acid were distributed in 28 cell lines derived from different histological classes of lung tumors as follows: