Abstract
An indigenous population of 450–500 beluga whales (Delphinapterus leucas) inhabiting the St. Lawrence Estuary has been exposed chronically for more than 50 years to a complex mixture of industrial pollutants including organochlorinated compounds (OC), polycyclic aromatic hydrocarbons (PAH) and heavy metals. From 1983 to 1990, we have necropsied 45 well preserved carcasses out of a total of 120 beluga whales reported dead over this period. Of these 45 animals, nine were affected by 10 malignant neoplasms. Fifteen animals (33%) were affected by pneumonia. Milk production was compromised in eight of 17 mature females (41%), by inflammatory changes (seven animals) and cancer (one animal) which affected the mammary glands. Opportunistic bacteria were found in pure culture, and/or in significant amounts in at least two organs in 20 belugas (44%). The concentrations of both total PCBs and highly chlorinated PCB congeners were much higher in St. Lawrence animals than in Arctic beluga whales. OC-induced immunosuppression has been repeatedly demonstrated in a wide variety of animal species. Therefore, it is probable that the immune functions of St. Lawrence beluga whales are impaired. Benzo[α]pyrene adducts were detected in 10 of the 11 St. Lawrence beluga whales of which tissues (six livers, 10/11 brains) were analyzed by a method based on HPLC. No such adducts were found in four Arctic animals. Since benzo[α]pyrene is one of the most potent chemical carcinogens known to man, these compounds might be responsible for some of the cancers observed in that population. Overall, our findings contrast vividly with those of others who found that cancers are exceedingly rare in free-ranging odontocete populations and that the major causes for mortalities in these populations are bacteria, parasites, and trauma.
Keywords: Beluga, Cancer, Cetaceans, Contaminants, DDT, Immunosuppression, Organochlorine, Pathology, PCB, Polycyclic Aromatic, Hydrocarbons, Whales
References
- 1.Reeves R.R., Mitchell E. Catch history and initial population of white whales (Delphinapterus leucas) in the river and Gulf of St. Lawrence, eastern Canada. Nat. Can. (Rev. Ecol. Syst.) 1984;111:63–121. [Google Scholar]
- 2.Béland P., Vezina A., Martineau D. Potential for growth of the St. Lawrence (Quebec, Canada) beluga whale (Delphinapterus leucas) population based on modelling. J. Cons. Ins. Explor. Mer. 1988;45:22–32. [Google Scholar]
- 3.Béland P., De Guise S., Plante R. Inst. Nat. Ecotoxicol. St. Laurent; Montréal: 1991. Toxicology and Pathology of St Lawrence Marine Mammals; pp. 1–95. (Report to the World Wildlife Fund). [Google Scholar]
- 4.Martineau D., Lagacé A., Massé R., Morin M., Béland P. Transitional cell carcinoma of the urinary bladder in a beluga whale (Delphinapterus leucas) Can. J. Vet. 1985;26:297–302. [PMC free article] [PubMed] [Google Scholar]
- 5.Martineau D., Lagacé A., Béland P., Desjardins C. Rupture of a dissecting aneurysm of the pulmonary trunk in a beluga whale (Delphinapterus leucas) J. Wildl. Dis. 1986;22:289–294. doi: 10.7589/0090-3558-22.2.289. [DOI] [PubMed] [Google Scholar]
- 6.Martineau D., Béland P., Desjardins C., Lagacé A. Levels of organochlorine chemicals in tissues of beluga whales (Delphinapterus leucas) from the St Lawrence Estuary, Quebec, Canada. Arch. Environ. Contam. Toxicol. 1987;16:137–147. [Google Scholar]
- 7.Martineau D., Lagacé A., Béland P., Higgins R., Armstrong D., Shugart L.R. Pathology of stranded beluga whales (Delphinapterus leucas) from the St Lawrence Estuary, Quebec. J. Comp. Pathol. 1988;98:287–311. doi: 10.1016/0021-9975(88)90038-2. [DOI] [PubMed] [Google Scholar]
- 8.Muir D.C.G., Ford C.A., Stewart R.E.A., Smith T.G., Addison R.F., Zinck M.E., Béland P. Organochlorine contaminants in belugas, Delphinapterus leucas, from Canadian waters. Can. Bull. Fish. Aquat. Sci. 1990;224:165–190. [Google Scholar]
- 9.Ray S., Dunn B.P., Payne J.F., Fancey L., Helbig R., Béland P. Aromatic DNA-carcinogen adducts in beluga whales (Delphinapterus leucas) from the Canadian arctic and the Gulf of St Lawrence. Mar. Pollut. Bull. 1991;22:392–396. [Google Scholar]
- 10.Béland P., Martineau D. In: Proceedings of the International Conference for Bio-indicators: Exposure and Effects. Shugart L.D., editor. Oak Ridge National Laboratory; Oak Ridge, Tennessee: 1991. [Google Scholar]
- 11.Wagemann R., Stewart R.E.A., Béland P., Desjardins C. Heavy metals and selenium in tissues of beluga whales, Delphinapterus leucas, from the Canadian Arctic and the St Lawrence estuary. Can. Bull. Fish. Aquat. Sci. 1990;224:191–206. [Google Scholar]
- 12.Norstrom R., Muir D.C.G., Ford C.A., Simon M., MacDonald C.R., Béland P. Classification of P-450 monooxygenase activities in beluga (Delphinapterus leucas) from patterns of PCB, PCDD and PCDF accumulation. Mar. Environ. Res. 1992;34:267–272. [Google Scholar]
- 13.Shugart L.R., Martineau D., Béland P. Presses Université du Québec; Sillery, Québec: 1990. Detection and quantitation of benzo(a)pyrene adducts in brain and liver tissues of beluga whales (Delphinapterus leucas) from the St. Lawrence and Mackenzie estuaries; pp. 219–223. [Google Scholar]
- 14.McConnell E., Hass J.R., Altman N., Moore J. A spontaneous outbreak of polychlorinated biphenyl (PCB) toxicity in Rhesus monkeys (Macaca mulatta): toxicopathology. Lab. Anim. Sci. 1979;29:666–673. [PubMed] [Google Scholar]
- 15.Safe S. Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs): biochemistry, toxicology, and mechanism of action. Crit. Rev. Immunol. 1984;13:319–395. doi: 10.3109/10408448409023762. [DOI] [PubMed] [Google Scholar]
- 16.Cowan D.R., Walker W.A., Brownell R.L., Jr. In: Research on Dolphins. Bryden M.M., Harrison R., editors. Oxford University Press; London: 1986. p. 323. Ch. 17. [Google Scholar]
- 17.Anon Toxic Chemicals in the Great Lakes and Associated Effects, Environment Canada, Fisheries and Oceans Canada, Health and Welfare Canada. Cat. No. En 37-94/1990-1E. 1991:65. Ottawa. [Google Scholar]
- 18.Cossa D., Rondeau J.G. Seasonal, geographical and size-induced variability in mercury content of Mytilus edulis in an estuarine environment: a reassessment of mercury pollution level in the Estuary and Gulf of St Lawrence. Mar. Biol. 1985;88:43–49. [Google Scholar]
- 19.Castonguay M., Dutil J.D., Desjardins C. Distinction between American eels (Anguilla rostrata) of different geographic origins on the basis of their organochlorine contaminant levels. Can. J. Fish. Aquat. Sci. 1989;46:836–843. [Google Scholar]
- 20.Smith J.N., Loring D.H. Geochronology for mercury pollution in the sediments of the Saguenay fjord, Quebec. Environ. Sci. Technol. 1981;15:944–951. doi: 10.1021/es00090a010. [DOI] [PubMed] [Google Scholar]
- 21.Martel L.M., Gagnon J., Massé R., Leclerc A., Tremblay L. Polycyclic aromatic hydrocarbons in sediments from the Saguenay fjord, Canada. Bull. Environ. Contam. Toxicol. 1986;37:133–140. doi: 10.1007/BF01607740. [DOI] [PubMed] [Google Scholar]
- 22.Pelletier E., Rouleau C., Canuel G. Niveau de contamination par le mercure des sediments de surface et des crevettes du fjord du Saguenay en 1985–1986. Rev. Int. Sci. Eau. 1989;2:13–27. [Google Scholar]
- 23.Goyer N. Ministère de l'Environnement, Gouvernement du Québec; Québec: 1980. Biphényles polychlorés, Bureau d'étude sur les Substances Toxiques; p. 18. [Google Scholar]
- 24.Goulet M., Laliberté D. Ministère de l'Environnement, Gouvernement du Québec; Québec: 1982. BPC: Contamination du milieu aquatique au Québec méridional, Direction générale des inventaires et de la recherche; p. 14. [Google Scholar]
- 25.Lamarche A. Environment Canada; Montreal: 1992. Quality of Water for Direct Human Consumption — St. Lawrence Update; pp. 1–100. [Google Scholar]
- 26.Paul M., Laliberté D. Ministère de l'Environnement, Gouvernement du Québec; Québec: 1988. Teneurs en mercure, plomb, cadmium, BPC et pesticides organochlorés des sédiments et de la chair des poissons du fleuve Saint-Laurent et de la rivière des Outaouais en 1985; pp. 1–80. [Google Scholar]
- 27.Roberts J.R., Rodgers D.W., Bailey J.R., Rorke M.A. Service de publications, CNRC/NRCC; Ottawa: 1979. Polychlorobiphenyles: critères biologiques pour évaluer leurs effets sur l'état de l'environnement; pp. 148–179. [Google Scholar]
- 28.Anon Panel on hazardous trace substances. Polychlorinated biphenyls — environmental impact. Environ. Res. 1972;5:249–362. [PubMed] [Google Scholar]
- 29.Sergeant D.E. Biology of white whales (Delphinapterus leucas) in western Hudson Bay. J. Fish. Res. Board Can. 1973;30:1065–1090. [Google Scholar]
- 30.Brodie P.F. The beluga (Delphinapterus leucas); growth at age based on a captive specimen and a discussion of factors affecting natural mortality estimates. Rep. Int. Whaling Commn. 1982;32:445–447. [Google Scholar]
- 31.Norstrom R.J., Simon M., Mulvihill M.J. A gel-permeation/column chromatography clean up method for the determination of TCDDs in animal tissue. Int. J. Environ. Anal. Chem. 1986;23:267–287. [Google Scholar]
- 32.Turle R., Norstrom R.J., Collins B. Comparison of PCB quantitation methods: re-analysis of archived specimens of herring gull eggs from the Great Lakes. Chemosphere. 1991;22:201–213. [Google Scholar]
- 33.Pelletier E., Béland P., Blouin N. Développement d'une méthode d'évaluation de l'impact des HAP sur les organismes aquatiques. Inst. Nat. Ecotoxicol. St-Laurent, Contr.: KA 313-9-3949. 1990:1–22. Montréal. [Google Scholar]
- 34.Shugart L.R., Holland J.M., Rahn R.O. Dosimetry of PAH skin carcinogenesis: covalent binding of benzo(a)pyrene to mouse epidermal DNA. Carcinogenesis. 1983;4:195–198. doi: 10.1093/carcin/4.2.195. [DOI] [PubMed] [Google Scholar]
- 35.Michaud R. Pêches et Océans Canada; Ottawa: 1993. Distribution estivale du béluga du Saint-Laurent; synthèse 1986 à 1992; p. 15. (Rapp. tech. can. sci. halieut. aquat. 1906). [Google Scholar]
- 36.Kingsley M.C.S., Hammill M.O. Pêches et Océans Canada; Ottawa: 1991. Photographic Census Surveys of the St. Lawrence Population, 1988 and 1990; pp. 1–19. (Rapp. tech. can. sci. halieut. aquat. 1776). [Google Scholar]
- 37.Michaud R., Vézina A., Rondeau N., Vigneault Y. Pêches et Océans Canada; Ottawa: 1990. Distribution annuelle et caractérisation préliminaire des habitats du béluga, Delphinapterus leucas, du Saint-Laurent; pp. 1–31. (Rapp. tech. can. sci. halieut. aquat. 1757). [Google Scholar]
- 38.Priester W.A., McKay F.W. Public Health Service. National Institutes of Health; Washington, DC: 1980. The Occurrence of Tumors in Domestic Animals; pp. 1–210. (National Cancer Institute. Monograph 54, U.S. Department of Health and Human Services). [PubMed] [Google Scholar]
- 39.Dorn C.R., Priester W.A. In: Veterinary Cancer Medicine. Theilen G.H., Madewell B.R., editors. Lea & Febiger; Philadelphia, PA: 1987. p. 27. Ch. 3. [Google Scholar]
- 40.Fowler M.E. In: Veterinary Cancer Medicine. Theilen G.H., Madewell B.R., editors. Lea and Febiger; Philadelphia, PA: 1987. p. 649. Ch. 24. [Google Scholar]
- 41.De Guise S., Lagacé A., Béland P. Tumors in twenty-four St. Lawrence beluga whales (Delphinapterus leucas) Vet. Pathol. 1991;31:444–449. doi: 10.1177/030098589403100406. [DOI] [PubMed] [Google Scholar]
- 42.Newell K.W., Ross A.D., Renner R.M. Phenoxy and picolinic acid herbicides and small intestinal adenocarcinoma in sheep. Lancet. 1984:1301–1305. doi: 10.1016/s0140-6736(84)90821-3. [DOI] [PubMed] [Google Scholar]
- 43.Béland P., De Guise S., Girard C., Lagacé A., Martineau D., Michaud R., Muir D.C.G., Norstrom R.J., Pelletier E., Ray S., Shugart L.R. Toxic compounds and health and reproductive effects in St. Lawrence beluga whales. J. Great Lakes Res. 1993;19:766–775. [Google Scholar]
- 44.Lutz W.K. In vivo covalent binding of organic chemicals to DNA as a quantitative indicator of chemical carcinogenisis. Mutat. Res. 1979;65:289–356. doi: 10.1016/0165-1110(79)90006-x. [DOI] [PubMed] [Google Scholar]
- 45.Davis D., Safe S. Immunosuppressive activities of polychlorinated dibenzofuran congeners: quantitative structure-activity relationship and interactive effects. Toxicol. Appl. Pharmacol. 1988;94:141–149. doi: 10.1016/0041-008x(88)90344-4. [DOI] [PubMed] [Google Scholar]
- 46.Poland A., Knutson J.C. 2,3,7,8,-tetrachlorodibenzo-p-dioxin and related halogenated hydrocarbons: examination of the mechanism of toxicity. Annu. Rev. Pharmacol. Toxicol. 1982;22:517–554. doi: 10.1146/annurev.pa.22.040182.002505. [DOI] [PubMed] [Google Scholar]
- 47.Andersson L., Nikolaidis E., Brunstrom B., Bergman A., Dencker L. Effects of polychlorinated biphenyls with Ah receptor affinity on lymphoid development in the thymus and the bursa of Fabricius of chick embryos in ovo. Toxicol. Appl. Pharmacol. 1991;107:183–188. doi: 10.1016/0041-008x(91)90342-c. [DOI] [PubMed] [Google Scholar]
- 48.Kerkvliet N.I., Baecher-Steppan L., Smith B.B., Youngberg J.A., Henderson M.C., Buhler D.R. Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): structure-activity relationships and effects in C57BI/6 mice congenic at the Ah locus. Fundam. Appl. Toxicol. 1990;14:532–541. doi: 10.1016/0272-0590(90)90257-k. [DOI] [PubMed] [Google Scholar]
- 49.Smialowicz R.J., Andrews J.E., Riddle M.M., Rogers R.R., Luebke R.W., Copeland C.B. Evaluation of the immunotoxicity of low level PCB exposure in the rat. Toxicology. 1989;56:197–211. doi: 10.1016/0300-483x(89)90133-9. [DOI] [PubMed] [Google Scholar]
- 50.Exon J.H., Talcott P.A., Koller L.D. Effect of lead, polychlorinated biphenyls and cyclophosphamide in rat natural killer cells, interleukin 2, and antibody synthesis. Fundam. Appl. Toxicol. 1985;5:158–164. doi: 10.1016/0272-0590(85)90060-0. [DOI] [PubMed] [Google Scholar]
- 51.Tryphonas H., Hayward S., O'Grady L., Loo J.C.K., Arnold D.L., Bryce F., Zawidzka Z.Z. Immunotoxicity studies of PCB (Aroclor 1254) in the adult Rhesus (Macaca mulatta) monkey — preliminary report. Int. J. Immunopharmacol. 1989;11:199–206. doi: 10.1016/0192-0561(89)90072-6. [DOI] [PubMed] [Google Scholar]
- 52.Loose L.D., Pittman K.A., Benitz K.F., Silkworth J.B. Polychlorinated biphenyl and hexachlorobenzene induced humoral immunosuppression. J. Reticuloendoth. Soc. 1977;22:253–271. [PubMed] [Google Scholar]
- 53.Thomas P.T., Hinsdill R.D. Effect of polychlorinated biphenyls on the immune response of rhesus monkeys and mice. Toxicol. Appl. Pharmacol. 1978;44:41–51. doi: 10.1016/0041-008x(78)90282-x. [DOI] [PubMed] [Google Scholar]
- 54.Loose L.D., Pittman K.A., Benitz K.-F., Silkworth J.B., Mueller W., Coulston F. Environmental chemical-induced immune dysfunction. Ecotoxicol. Environ. Saf. 1978;2:173–198. doi: 10.1016/0147-6513(78)90008-8. [DOI] [PubMed] [Google Scholar]
- 55.Shigematsu N., Norimatsu Y., Ishibashi T., Yoshida M., Suetsugu S., Kawatsu T., Ikeda T., Saito R., Ishimaru S., Shirakusa T., Kido M., Emori K., Toshimitsu H. Clinical and experimental studies on impairment of respiratory organs in chlorobiphenyl poisoning. Fukuoka Acta Med. 1971;62:150. [Google Scholar]
- 56.Wasserman D., Wasserman M., Cucos S., Djavaherian M. Function of adrenal gland zona fasciculata in rats receiving polychlorinated biphenyls. Environ. Res. 1973;6:334–338. doi: 10.1016/0013-9351(73)90045-5. [DOI] [PubMed] [Google Scholar]
- 57.Durham S.K., Brouwer A. 3,4,3′,4′-tetrachlorobiphenyl distribution and induced effects in the rat adrenal gland. Localization in the zona fasciculata. Lab. Invest. 1990;62:232–239. [PubMed] [Google Scholar]
- 58.Chu I., Villeneuve D.C., Secours V., Valli V.E. Toxicological assessment of chlorinated diphenyl ethers in the rat. J. Environ. Sci. Health. 1990;25:225–241. doi: 10.1080/03601239009372686. [DOI] [PubMed] [Google Scholar]
- 59.Imanishi J., Nomura H., Matsubara M., Kita M., Won S.-J., Mizutani T., Kishida T. Effect of polychlorinated biphenyl on viral infections in mice. Infect. Immunol. 1980;29:275–277. doi: 10.1128/iai.29.1.275-277.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60.Koller L.D., Thigpen J.E. Biphenyl-exposed rabbits. Am. J. Vet. Res. 1973;34:1605–1606. [PubMed] [Google Scholar]
- 61.Friend M., Trainer D.O. Polychlorinated biphenyl: interaction with duck hepatitis virus. Science. 1970;170:1314–1316. doi: 10.1126/science.170.3964.1314. [DOI] [PubMed] [Google Scholar]
- 62.Koller L.D. Enhanced polychlorinated biphenyl lesions in Moloney leukemia virus-infected mice. Clin. Toxicol. 1977;11:107–116. doi: 10.3109/15563657708989824. [DOI] [PubMed] [Google Scholar]
- 63.Krzystyniak K., Bernier J., Hugo P., Fournier M. Suppression of MHV-3-activated macrophages by dieldrin. Biochem. Pharmacol. 1986;35:2577–2586. doi: 10.1016/0006-2952(86)90056-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64.White K.L., Lysy H., McCoy J.A., Anderson A.C. Modulation of serum complement levels following exposure to polychlorinated dibenzo-p-dioxins. Toxicol. Appl. Pharmacol. 1986;84:209–219. doi: 10.1016/0041-008x(86)90128-6. [DOI] [PubMed] [Google Scholar]
- 65.Britt J.O., Howard E.B. In: Pathobiology of Marine Mammal Diseases. Howard E.B., editor. CRC Press; Boca Raton, FL: 1983. p. 80. Ch. 4. [Google Scholar]
- 66.Kannan N., Tanabe S., Ono M., Tatsukawa R. Critical evaluation of polychlorinated biphenyl toxicity in terrestrial and marine mammals: increasing impact of non-ortho and mono-ortho coplanar polychlorinated biphenyls from land to ocean. Arch. Environ. Contam. Toxicol. 1989;18:850–857. doi: 10.1007/BF01160300. [DOI] [PubMed] [Google Scholar]
- 67.Cavagnolo R.Z. The immunology of marine mammals. Dev. Comp. Immunol. 1979;3:245–257. doi: 10.1016/s0145-305x(79)80022-1. [DOI] [PubMed] [Google Scholar]
- 68.Simpson J.G., Gardner M.B. In: Mammals of the Sea: Biology and Medicine. Ridgway S.H., editor. Thomas; Springfield, IL: 1972. p. 298. Ch. 5. [Google Scholar]
- 69.Waxler G.L., Drees D.T. Comparison of body weights, organ weights and histological features of selected organs of gnotobiotic, conventional and isolator-reared contaminated pigs. Can. J. Comp. Med. 1972;36:265–274. [PMC free article] [PubMed] [Google Scholar]
- 70.Luckey T.D. Academic Press; New York: 1963. Germfree Life and Gnotobiology; p. 360. [Google Scholar]
- 71.Thorbecke G.J. Some histological and functional aspects of lymphoid tissue in germfree animals. Ann. N.Y. Acad. Sci. 1959;78:237–246. doi: 10.1111/j.1749-6632.1959.tb53106.x. [DOI] [PubMed] [Google Scholar]
- 72.Geraci J.R., St. Aubin D.J., Barker I.K., Webster R.G., Hinshaw V.S., Bean W.J., Ruhnke H.L., Prescott J.H., Early G., Baker A.S., Madoff S., Schooley R.T. Mass mortality of harbor seals: pneumonia associated with influenza A virus. Science. 1982;215:1129–1131. doi: 10.1126/science.7063847. [DOI] [PubMed] [Google Scholar]
- 73.Kennedy S., Smyth J.A., Cush P.F., McAliskey M., McCullough S.J., Rima B.K. Histopathologic and immunocytochemical studies of distemper in harbor porpoises. Vet. Pathol. 1991;28:1–7. doi: 10.1177/030098589102800101. [DOI] [PubMed] [Google Scholar]
- 74.Domingo M., Visa J., Pumarola M., Marco A.J., Ferrer L., Rabanal R., Kennedy S. Pathologic and immunocytochemical studies of morbillivirus infection in striped dolphins (Stenella coeruleoalba) Vet. Pathol. 1992;29:1–10. doi: 10.1177/030098589202900101. [DOI] [PubMed] [Google Scholar]
- 75.Domingo M., Ferrer L., Pumarola M., Marco A., Plana J., Kennedy S., McAliskey M., Rima B. Morbillivirus in dolphins. Nature. 1990;348:21. doi: 10.1038/348021a0. [DOI] [PubMed] [Google Scholar]
- 76.Duignan P.J., Geraci J.R. Epizootiology of marine mammal morbilliviruses in the western north Atlantic. Tenth Biennial Conference on the Biology of Marine Mammals; Galveston; 11–15 November, 1993. [Google Scholar]
- 77.Eis D. Simplification in the etiology of recent seal deaths. Ambio. 1989;18:144. [Google Scholar]
- 78.Cook F.R., Muir D. The committee on the status of endangered wildlife in Canada (COSEWIC): history and progress. Nat. Can. (Rev. Ecol. Syst.) 1984;98:63–70. [Google Scholar]
- 79.O'Brien S.J., Goldman D., Merril C.R., Bush M. The cheetah is depauperate in genetic variation. Science. 1983;221:459–461. doi: 10.1126/science.221.4609.459. [DOI] [PubMed] [Google Scholar]
- 80.O'Brien S.J., Roelke M.E., Marker L., Newman A., Winkler C.A., Meltzer D., Colly L., Evermann J.F., Bush M., Wildt D.E. Genetic basis for species vulnerability in the cheetah. Science. 1985;227:1428–1434. doi: 10.1126/science.2983425. [DOI] [PubMed] [Google Scholar]
- 81.Yuhki N., O'Brien S.J. Vol. 87. 1990. DNA variation of the mammalian major histocompatibility complex reflects genomic diversity and population history; pp. 836–840. (Proc. Natl. Acad. Sci.). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82.Patenaude N., White B. Reduced genetic variability of the Saint Lawrence beluga whale population as assessed by DNA fingerprinting. Mol. Ecol. 1994;3 doi: 10.1111/j.1365-294x.1994.tb00077.x. in press. [DOI] [PubMed] [Google Scholar]
- 83.Loft S.K., Vistisen M., Wertz A., Tjonneland K., Overvad K., Poulsen H.E. Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis. 1992;13:2241–2247. doi: 10.1093/carcin/13.12.2241. [DOI] [PubMed] [Google Scholar]
- 84.Zimmer D.M., Aaron C.S., O'Neill J.P., Albertini R.J. Enumeration of 6-thioguanine-resistant T-lymphocytes in the peripheral blood of nonhuman primates (Cynomolgus monkeys) Environ. Mol. Mutagenesis. 1991;18:161–167. doi: 10.1002/em.2850180304. [DOI] [PubMed] [Google Scholar]
- 85.Nicklas J.A., Hunter T.C., O'Neil J.P., Albertini R.J. Molecular analyses of in vivo hprt mutations in human T-lymphocytes. III. Longitudinal study of hprt gene structural alterations and T-cell clonal origins. Mutat. Res. 1989;215:147–160. doi: 10.1016/0027-5107(89)90178-4. [DOI] [PubMed] [Google Scholar]
- 86.Albertini R.J., Nicklas J.A., O'Neil J.P. Studies of DNA alterations in in vivo somatic cell mutations in humans. Basic Life Sci. 1990;53:315–328. doi: 10.1007/978-1-4613-0637-5_25. [DOI] [PubMed] [Google Scholar]
- 87.Albertini R.J., O'Neill J.P., Nicklas J.A., Recio L., Skopek T.R. hprt mutations in vivo in human T-lymphocytes: frequencies, spectra and clonality. Prog. Clin. Biol. Res. 1990;340C:15–24. [PubMed] [Google Scholar]
- 88.Ostrosky-Wegman P., Montero R., Palao A., Cortinas de Nava C., Hurtado F., Albertini R.J. 6-Thioguanine-resistant T-lymphocyte autoradiographic assay. Determination of variation frequencies in individuals suspected of radiation exposure. Mutat. Res. 1990;232:49–56. doi: 10.1016/0027-5107(90)90109-h. [DOI] [PubMed] [Google Scholar]
- 89.O'Neil J.P., Sullivan L.M., Albertini R.J. In vitro induction, expression and selection of thioguanine-resistant mutants with human T-lymphocytes. Mutat. Res. 1990;240:135–142. doi: 10.1016/0165-1218(90)90017-v. [DOI] [PubMed] [Google Scholar]
- 90.Jenner N.K., Ostrander G.K., Kavanagh T.J., Livesey J.C., Shen M.W., Kim S.C., Holmes E.H. A flow cytometric comparison of DNA content and glutathione levels in hepatocytes of English sole (Parophyrs vetulus) from areas of differing water quality. Arch. Environ. Contam. Toxicol. 1990;19:807–815. doi: 10.1007/BF01055045. [DOI] [PubMed] [Google Scholar]
- 91.Jones P.A., Buckley J.D., Henderson B.E., Ross R.K., Pike M.C. From gene to carcinogen: a rapidly evolving field in molecular epidemiology. Cancer Res. 1991;51:3617–3620. [PubMed] [Google Scholar]
- 92.Ozonoff D., Longnecker M.P. Epidemiologic approaches to assessing human cancer risk from consuming aquatic food resources from chemically contaminated water. Environ. Health Perspect. 1991;90:141–146. doi: 10.1289/ehp.90-1519480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 93.Fox G.A. Practical causal inference for ecoepidemiologists. J. Toxicol. Environ. Health. 1991;33:359–373. doi: 10.1080/15287399109531535. [DOI] [PubMed] [Google Scholar]
- 94.Jensen R.H., Bigbee W.L., Langlois R.G. Multiple endpoints for somatic mutations in humans provide complementary views for biodosimetry, genotoxicity and health risks. Prog. Clin. Biol. Res. 1990;340C:81–92. [PubMed] [Google Scholar]
- 95.Girard C., Lagacé A., Higgins R., Béland P. Adenocarcinoma of the salivary gland in a beluga whale (Delphinapterus leucas) J. Vet. Diagn. Invest. 1991;3:264–265. doi: 10.1177/104063879100300317. [DOI] [PubMed] [Google Scholar]
- 96.Anonymous . Canadian Centre for Health Information; Ottawa: 1991. (Health Reports. Suppl. No. 8. Vol. 3. No. 2., Cancer in Canada. 1985, 1986, Statistics Canada). [Google Scholar]
- 97.Anonymous . Institut national du cancer du Canada; Toronto, Canada: 1992. Statistiques canadiennes sur le cancer, 1992; pp. 1–65. [Google Scholar]
- 98.Priester W.A., Mantel N. Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J. Natl. Cancer Inst. 1971;47:1333–1344. [PubMed] [Google Scholar]
- 99.Bristol D., Baum K.H., Mezza L.E. Adenocarcinoma of the jejunum in two cows. J. Am. Vet. Med. Assoc. 1984;185:551–553. [PubMed] [Google Scholar]
- 100.Georgsson G., Vigfusson H. Carcinoma of the small intestine of sheep in Iceland. A pathological and epizootiological study. Acta Vet. Scand. 1973;14:392–409. doi: 10.1186/BF03547427. [DOI] [PMC free article] [PubMed] [Google Scholar]