JNCI: Journal of the National Cancer Institute

Meigs, J., Wister;Marrett, Loraine, D.;Ulrich, Franziska, U.;Flannery, John, T.

doi: 10.1093/jnci/76.1.1pmid: N/A

Abstract Linkage with records of the Connecticut Tumor Registry was used to determine cancer incidence in a cohort of workers (n = 984) at a benzidine manufacturing facility. Compared to the findings for the Connecticut population, there was a statistically significant excess of bladder tumor among male cohort members [standardized incidence ratio (SIR)=343; 95% confidence limits (CL) = 148, 676; n = 830], which was confined to those with the highest estimated level of benzidine exposure (SIR = 1,303; CL=479, 2,839; n = 105). No significantly elevated risks were found for cancers at other anatomic sites in men or at any anatomic sites in women; nor was there any pattern of increasing risk with increasing benzidine exposure for sites other than bladder. In addition, the elevated bladder cancer risk was greater for men first employed during the earliest years of the plant, namely, 1945–49 (SIR = 976; CL=262, 2,498) as compared to those first employed in 1950–54 (SIR=213; CL=3, 1,184) after equalization of duration of follow-up. These results suggest that the major preventive measures instituted around 1950 may have reduced bladder cancer risk in this plant. 2 Supported by Public Health Service contracts N01CP-33235 and N01CP-61002 from the Division of Cancer Cause and Prevention, National Cancer Institute; by the Institute of Occupational Medicine and Hygiene, Yale University School of Medicine; and by the Upjohn Co. L. D. M. is currently supported by a National Health Research Scholar Award from the National Health Research and Development Program, Health and Welfare Canada. 3 Research procedures were in accord with the ethical standards of the Human Investigations Committee, Yale University School of Medicine, and Connecticut Department of Health Services. This content is only available as a PDF. Author notes 4 Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St., New Haven, CT 06510. 5 Connecticut Cancer Epidemiology Unit, Yale University School of Medicine. 6 Present addresses: Ontario Cancer Treatment and Research Foundation and University of Toronto, Toronto, ON, Canada. 7 Present address: 28 Coginchaug Ct., Guilford, CT 06437. 8 Connecticut Tumor Registry, Connecticut Department of Health Services, 150 Washington St., Hartford, CT 06106. 9 We thank Mrs. JoAnn Kelly and Mrs. Jean Heston of the Connecticut Cancer Epidemiology Unit for programming help and for provision of demographic and cancer data, respectively.

Kimmel, Kathryn, A.;Carey, Thomas, E.;Judd, W., John;McClatchey, Kenneth, D.

doi: 10.1093/jnci/76.1.9pmid: N/A

Abstract The IgM monoclonal antibody G10 was raised against the human squamous cell carcinoma (SCC) cell line UM-SCC-1. In initial screening against cultured cells, G10 bound to 2 SCC lines (UM-SCC-1 and UM-SCC-13) and 1 pancreatic carcinoma line (UM-PAd-1) but not to cultured fibroblasts (WI-38), ovarian carcinoma cells (SK-OV-3), or malignant melanoma cells (SK-MEL-28 and MeWo). In subsequent tests against cultured cell lines, G10 gave positive reactions with 30 of 33 SCC lines but only 4 of 29 non-SCC lines. The non-SCC lines that bound G10 were UM-PAd-1, 2 transitional cell carcinoma lines (T24 and RT4), and 1 melanoma line (SK-MEL-22). When tested against cultures derived from normal skin or mucosa, G10 was reactive with the epithelioid squamous cells but not with the fibroblasts in each culture. The antigen defined by antibody G10 was stable to fixation with Formalin, and its distribution in tissue sections was examined with the use of immunoperoxidase assays. All SCC biopsy specimens examined in this way were reactive with antibody G10. In similar tests against sections of fixed normal tissues, G10 stained the superficial squamous cells of the epidermis and the basal and suprabasal layers of mucosal squamous epithelial cells from the esophagus. All layers of the laryngeal epithelium were positive. Endothelial cells and certain glandular cells were also positive for G10 binding. G10 agglutinated human red blood cells of all blood groups except those from individuals of the Bombay group (Oh) who lack the H blood group determinant. Against defined oligosaccharides, G10 bound strongly only to the monofucosyl H type 2 structure and was slightly cross-reactive with the synthetic difucosyl H type 2 or Y structure. These results are consistent with previous reports of blood group antigen tissue distribution and indicate that the H type 2 determinant is expressed by all or nearly all mucosal squamous cancers. Less frequent expression by cells of other tumor types may correlate with tissue-specific activation of the H gene-specified fucosyltransferase. 2 Supported by Public Health Service (PHS) Biomedical Research Support Grant RR-05383 from the Division of Research Resources, National Institutes of Health; and by PHS grants CA-28564 and CA-35929 from the Division of Extramural Activities, National Cancer Institute (NCI). This content is only available as a PDF. Author notes 3 Cancer Research Laboratory, Department of Otolaryngology/Head and Neck Surgery, and Department of Microbiology and Immunology, The University of Michigan, School of Medicine, Ann Arbor, MI 48109. 4 Present address: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, MD 20892. 5 Predoctoral fellow of the PHS Genetics Training Grant T32GM-07544 from the National Institute of General Medical Sciences. 7 Recipient of PHS Research Career Development Award CA-00621 from the Division of Extramural Activities, NCI. 8 Department of Pathology, The University of Michigan, School of Medicine. 9 We are indebted to the scientists at Chembiomed, Ltd., for performing the G10 binding assays with synthetic oligosaccharides. We appreciate the patience and expert typing assistance of Ms. Judith Jacobs, Ms. Carol Perrault, Ms. Cassandra Richardson, and Ms. Francine Hume.

Dodds,, Linda;Davis,, Scott;Polissar,, Lincoln

doi: 10.1093/jnci/76.1.21pmid: N/A

Abstract All incident cases of microscopically confirmed lung cancer diagnosed between 1974 and 1981 in western Washington State were identified through the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, Bethesda, MD. The incidence of lung cancer by histologic type was studied in relation to time, with age, sex, and stage of disease at diagnosis being taken into account. Overall and within each sex, the incidence of adenocarcinoma has increased significantly since 1974. The rate of increase has been higher among females (86% increase) than among males (54% increase), with most of the increase in both sexes being among those over age 65 years with distant or unstaged disease at diagnosis. Similar patterns were not observed for squamous cell carcinoma. The potential effects of changes in diagnostic and pathology practice during the study period in producing these results were explored, and etiologic implications of the observed increase in adenocarcinoma were discussed. This content is only available as a PDF. Author notes 2 Division of Public Health Sciences, Program in Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA 98104; and Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195. 4 Division of Public Health Sciences, Program in Epidemiology, Fred Hutchinson Cancer Research Center; and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington. 5 We thank Dr. Peter W. Wright for providing the initial impetus for this project, Dr. Nancy Kreiger for her helpful comments and advice, Dr. Kenneth Kopecky and Dr. Dale Preston for their assistance with the Poisson regression analysis, and Ms. Yukiko Uehara for her assistance in preparing this manuscript.

Frederick Li,, P.;Jamison, Deborah, S.;Meadows, Anna, T.

doi: 10.1093/jnci/76.1.31pmid: N/A

Abstract Usefulness of an etiologic questionnaire was examined in an interview study of 503 children with cancer. The medical records of the children were abstracted, and their parents responded to a questionnaire-interview to identify genetic and environmental causes of cancer. Among 1,123 siblings of the index patients, 10 developed cancer as compared with 2 expected on the basis of cancer rates for the general population. Cancer risk factors were identified in individual patients with predisposing genetic and congenital disorders: neurofibromatosis (brain tumor), hereditary immunodeficiency (lymphoma), Down's syndrome (leukemia), XY gonadal dysgenesis (germ cell tumor), giant nevus (melanoma), and meningocele (sacral teratocarcinoma). Environmental causes of childhood cancer were difficult to discern because prior exposures were numerous, diverse, and usually ill defined. The questionnaire yielded more data than the medical record on gestational and family history and helped identify patients with exceptionally high cancer risk for additional investigation. Although the findings provide anecdotal confirmation of several associations, few original etiologic hypotheses were generated for formal testing with conventional epidemiologic techniques. This content is only available as a PDF. Author notes 2 Division of Epidemiology and Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115. 3 Clinical Studies Section, Clinical Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, MD 20892. 5 Recipient of the Amy Potter Memorial Fellowship. 6 The Children's Hospital of Philadelphia, PA 19104. 7 We thank Mr. David Marchetto for assistance in data collection, Ms. Kathreen Gimbrere for editorial assistance, and Ms. Carol Lovely for secretarial work.

Fountzilas,, George;Gratzner,, Howard;Lim, Lori, O.;Yunis, Adel, A.

doi: 10.1093/jnci/76.1.37pmid: N/A

Abstract The inhibitory effect of several drug combinations on the growth of the human pancreatic carcinoma cell line MIA PaCa-2 was studied in relation to drug-scheduling interval in vitro. All drug exposures were for 1 hour. The sequential exposure of cells to 1.5×10−8M vincristine (VCR) or vindesine (VDS) followed by 2×10−8M 1,2-dihydroxy-9,10-anthracenedione (DHAD) or 3×10−7M adriamycin (ADR) had at best an additive effect, demonstrated by isobologram analysis, when the two drugs were given 6 hours apart. Flow cytometry (FCM) analysis after exposure of the cells to the priming drug alone, i.e., VCR or VDS, showed an accumulation of cells in S-phase. The exposure of MIA PaCa-2 cells to 1.6×10−5M 5-fluorouracil (FUra) followed by 2×10−8M DHAD or 3×10−7M ADR had an additive (with DHAD) or synergistic (with ADR) effect when the two drugs were given simultaneously and a synergistic effect with either drug when they were given 2, 6, or 24 hours apart. FCM analysis after exposure to FUra alone showed a rapid S-phase accumulation appearing within 6 hours and increasing further after 24 hours. Sequential exposure of cells to 1.5×10−8M VCR and 1.6×10−5M FUra had a synergistic effect, regardless of the sequence or the time interval between the two drugs. 2 Supported in part by a gift from Mr. Issam Fares, by Public Health Service grant 07114, and by a gift from Mrs. Dolores Lourcey. This content is only available as a PDF. Author notes 3 Department of Medicine (R-38), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101. 4 Institute for Cell Analysis, University of Miami School of Medicine. 5 Department of Biochemistry, University of Miami School of Medicine. 6 Department of Oncology, University of Miami School of Medicine. 8 We are indebted to Mr. Mario Saldana for the examination of the histologic sections from MIA PaCa-2 xenografts and to Dr. T. S. Anantha Samy, Department of Oncology and the Comprehensive Cancer Center, University of Miami School of Medicine, for his critical review.

Ross,, Ronald;Bernstein,, Leslie;Judd,, Howard;Hanisch,, Rosemarie;Pike,, Malcolm;Henderson,, Brian

doi: 10.1093/jnci/76.1.45pmid: N/A

Abstract Blacks in the United States have the highest prostate cancer rate in the world and nearly twice that of whites in the United States. The 2:1 black-to-white ratio in prostate cancer rates is already apparent at age 45 years, the age at which the earliest prostate cancer cases occur. This finding suggests that the factor(s) responsible for the difference in rates occurs, or first occurs, early in life. Testosterone has been hypothesized to play a role in the etiology of prostate cancer, because testosterone and its metabolite, dihydrotestosterone, are the principal trophic hormones that regulate growth and function of epithelial prostate tissue. This report gives the results of assays of circulating steroid hormone levels in white and black college students in Los Angeles, CA. Mean testosterone levels in blacks were 19% higher than in whites, and free testosterone levels were 21% higher. Both these differences were statistically significant. Adjustment by analysis of covariance for time of sampling, age, weight, alcohol use, cigarette smoking, and use of prescription drugs somewhat reduced the differences. After these adjustments were made, blacks had a 15% higher testosterone level and a 13% higher free testosterone level. A 15% difference in circulating testosterone levels could readily explain a twofold difference in prostate cancer risk. 2 Supported in part by Public Health Service grants CA-33512 and CA-00652 from the National Cancer Institute. This content is only available as a PDF. Author notes 3 Department of Preventive Medicine, School of Medicine, University of Southern California, Los Angeles, CA 90033. 4 Department of Obstetrics and Gynecology, School of Medicine, University of California at Los Angeles, Los Angeles, CA 90024. 5 Cancer Epidemiology and Clinical Trials Unit, Imperial Cancer Research Fund, Oxford, England OX26HE.

Mack, Thomas, M.;Yu, Mimi, C.;Hanisch,, Rosemarie;Henderson, Brian, E.

doi: 10.1093/jnci/76.1.49pmid: N/A

Abstract Four hundred and ninety pancreas cancer patients representative of confirmed cases in Los Angeles County residents of working age were compared to healthy controls individually matched by age, sex, race, and neighborhood. Home interviews were conducted on occupation, smoking, food and beverage consumption, and medical history. Cigarette smoking was a strong and consistent predictor of pancreas cancer occurrence; the effect disappeared after a decade of nonsmoking, and there was no increase in risk among current smokers as daily dose increased. There was no link between pancreas cancer and past consumption of tea, carbonated beverages, beer, or spirits; and an association with coffee consumption was inconsistent. A strong association between pancreas cancer and history of subtotal gastrectomy at any past time could not be explained by chance or any other factor. Pancreas cancer patients had experienced fewer allergies of any kind. 2 Supported by Public Health Service grants P01CA-17054 and R01CA-19171 from the Division of Extramural Activities, National Cancer Institute. This content is only available as a PDF. Author notes 3 Department of Preventive Medicine, School of Medicine, University of Southern California, Los Angeles, CA 90033. 5 We thank Ms. Neeltje M. Mack for her technical assistance in the preparation of this paper.

Valeriote,, Frederick;Grates,, Harry

doi: 10.1093/jnci/76.1.61pmid: N/A

Abstract The murine tumor MOPC-315 plasmacytoma was studied as a model for human multiple myeloma. Plasmacytoma cells (106) were injected iv into BALB/c mice, and 14 days later a single ip dose of the anticancer agent to be tested was administered at a dose that would result in 10% toxicity within 30 days (LD10). Increases in life-span and cures resulting from the LD10 dose were the parameters assessed. The response of this MOPC-315 plasmacytoma model to a variety of anticancer agents demonstrated good correlation with clinically active agents. A number of investigational agents were found to be highly active and potential candidates for clinical phase II studies. 2 Supported by Public Health Service grant CA-34140 from the National Cancer Institute and by a grant from the Wayne State University Ken Kasle Trust for Cancer Research. This content is only available as a PDF. Author notes 3 Department of Medicine, Division of Oncology, Wayne State University, P.O. Box 02188, Detroit, MI 48201; and Department of Experimental Therapeutics, Michigan Cancer Foundation, Detroit, MI 48201.

Pour, Parviz, M.;Birt, Diane, F.

doi: 10.1093/jnci/76.1.67pmid: N/A

Abstract For assessment of the effect of dietary protein on spontaneous diseases and on the carcinogenicity of N-nitrosobis(2-oxopropyl)amine [(BOP) CAS: 60599-38-4], Syrian golden hamsters were fed either low protein (LP; 9% casein), medium protein (MP; 18% casein), or high protein (HP; 36% casein) in a diet containing a medium fat (corn oil) level. The experimental design permitted distinguishing between the effects of protein levels on initiation and development of various lesions in hamsters, in comparison with a control group that was given MP diet for life. When fed after BOP treatment, HP diet inhibited, among induced tumors, pulmonary adenomas in males. Among spontaneous diseases, LP diet fed before 8 weeks of age enhanced colitis in both males and females, renal and adrenal gland amyloidosis in males, and gastric vascular calcinosis in males but inhibited liver abscesses and liver cysts in both males and females. When fed after 8 weeks of age, LP diet enhanced gastric and renal vascular calcification and parathyroid gland adenomas in both sexes but inhibited hepatic, renal, and adrenal gland amyloidosis in females and liver abscesses and liver cysts in both males and females. The feeding of HP diet before 8 weeks of age enhanced the development of colitis and adrenal gland lipomatosis in both males and females but inhibited the development of adrenal gland amyloidois and adrenal cortical cell hyperplasia in males. When fed to hamsters after 8 weeks of age, HP diet increased the incidence of adrenal gland amyloidosis in females and colitis in both males and females but reduced the frequency of liver cysts in both males and females and of adrenal cortical cell hyperplasia in males. The overall data and literature review indicate that the effect of dietary protein on tumorigenesis is tissue, sex, species, and strain related. 2 Supported by Public Health Service contract N01CP-33278 from the Division of Cancer Cause and Prevention, National Cancer Institute. 3 Animals were maintained under the guidelines set forth by the Eppley Institute for Research in Cancer and Allied Diseases and by the National Research Council. This content is only available as a PDF. Author notes 4 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 42d and Dewey Ave., Omaha, NE 68105. 5 Department of Pathology and Microbiology, University of Nebraska Medical Center. 6 We thank Ms. Kathy Stepan for excellent technical assistance and Ms. Mardelle Susman for editorial aid.

Smith, Garry, J.;Bennett, Frances, A.;Steele, John, G.;Bentel, Jacqueline, M.

doi: 10.1093/jnci/76.1.73pmid: N/A

Abstract Prolonged culture of NAL1A in 1 μM dexamethasone (CAS: 50-02-2) at low passage numbers resulted in the emergence of a morphologically altered and malignant cell strain, NAL1AM. (NAL1A was derived from lungs of normal adult female inbred BALB/c mice and exhibits several characteristics of epithelial cells.) A clone of NAL1A, B5, was shown to undergo a spontaneous morphologic alteration during culture in normal medium to resemble NAL1AM and cells of NUL1, a strain cultured directly from urethane (CAS: 51-79-6)-induced adenomas of mouse lung. Whereas NAL1A did not form colonies in soft agar, the clone B5 of NAL1A as well as NAL1AM and NUL1 showed quite high anchorage-independent growth (colony-forming efficiency, 6.3–7.8%). Compared with NAL1A cells, clone B5, NAL1AM, and NUL1 each exhibited a ninefold-reduced level of cellular binding of epidermal growth factor. 2 Supported by a grant from the National Health and Medical Research Council of Australia (NH&MRC). This content is only available as a PDF. Author notes 3 Unit of Cellular and Molecular Biology, School of Pathology, The University of New South Wales, P.O. Box 1, Kensington, New South Wales, 2033 Australia. 4 Research Fellow of the NH&MRC. 5 Commonwealth Scientific and Industrial Research Organization Division of Molecular Biology, North Ryde, New South Wales, 2113 Australia. 6 We thank Dr. G. Todaro for generously supplying the A431 cell line and Dr. R. H. Whitehead, Ludwig Institute for Cancer Research, Melbourne, for the rabbit anti-human prekeratin. We gratefully acknowledge M. de Montfort, C. Mudge, and S. Watkins for excellent technical assistance and Mrs. A. McGill for preparing the manuscript.