Sprague-Dawley rats were exposed to 0, 26, or 2600 ppm lead as lead acetate in drinking water for 76 weeks. At 28 weeks of lead exposure, a portion of each group was exposed simultaneously to 6.36 g/kg ethyl urea (EU) and 2.0 g/kg sodium nitrite (NaNO2) for a duration of 20 weeks, and then continued an additional 28 weeks on standard diet free of EU and NaNO2. The animals were observed for incidence, latency, and distribution of tumors. Rats exposed to 2600 ppm lead alone had 81% renal tumors, while rats given 2600 ppm lead in combination with EU/NaNO2 had a 50% incidence. Renal tumors did not occur in the EU/NaNO2 only or EU/NaNO2-26 ppm lead groups. The major tumor type found in EU/NaNO2-exposed rats was lymphosarcoma. ***Lead did not appear to be syncarcinogenic to the activity of ethylnitrosourea, the carcinogen formed by oral exposure to EU and NaNO2. The lead-induced renal neoplasms were histologically similar to those which occur spontaneously in man and, therefore, may serve as an animal model to study human disease.
References
1.
1. Bard JC (1973). Effect of sodium nitrite and sodium nitrate on butulinal toxin production and nitrosamine formation in weiners. Proceedings of the Meat Industry Research Conference.American Meat Institute Foundation, Chicago, pp. 61–68.
2.
2. Boyland E, Dukes CE, Gover PL, and Mitchley BC (1962). The induction of renal tumors by feeding lead acetate to rats.Br. J. Cancer16: 283–288.
3.
3. Brunnemann KD, Yu L, and Hoffman D (1977). Assessment of Carcinogenic volatile N-nitrosamines in tobacco and in mainstream and sidestream smoke from cigarettes.Cancer Res.37: 3218–3222.
4.
4. Caprio RJ, Margulis HL, and Joselow MM (1974). Lead absorption in children and its relationship to urban traffic densities. Arch. Environ.Health28: 195–201.
5.
5. Druckrey H, Ivankovic S, and Preussman R (1966). Teratogenic and carcinogenic effects in the of fspring after single injection of ethylnitrosourea in pregnant rats.Nature210: 1378–1379.
6.
6. Elespuru RK and Lijinsky W (1973). The formation of carcinogenic nitroso compounds from nitrite and some types of agricultural chemicals.Food Cosmet. Toxicol.11: 807–817.
7.
7. Exon JH, Talcott PA, and Koller LD (1985). Effect of lead, polychlorinated biphenyls, and cyclophosphamide on rat natural killer cells, interleukin 2 and antibody synthesis.Fundam. Appl. Toxicol.5: 158–164.
8.
8. Fine DH, Ross R, and Rounbehler DP (1977). Formation in vivo of volatile N-nitrosamines in man after ingestion of cooked bacon and spinach.Nature265: 753–757.
9.
9. Fine DH and Rounbehler DP (1976). N-Nitroso compounds in water. In: Identification and Analysis of Organic Pollutants in Water, LH Keith (ed). Ann Arbor Science Publ., Ann Arbor, MI, pp. 255–263.
10.
10. Fine DH, Rounbehler DP, Belcher NM, and Epstein SS (1976). N-Nitroso compound; detection in ambient air.Science192: 1328–1330.
11.
11. Furst A, Schlauder M, and Sasmore DP (1976). Tumorigenic activity of lead chromate.Cancer Res.36: 1779–1783.
12.
12. Gainer JH (1973). Activation of the Rauscher leukemia virus by metals.J. Natl. Cancer Inst.51: 609–613.
13.
13. Greenberg RA (1972). Nitrite in the control of Clostridium botulinum. Proceedings of the Meat Industry Research Conferences. American Meat Institute Foundation, Chicago, pp. 25–34.
14.
14. Haley TJ (1968). A review of the toxicology of lead. In: Air Quality Monograph 69-7. American Petroleum Institute, New York, p. 53.
15.
15. Hass GM, McDonald JH, Oyasn R, Battiform HA, and Palouchek JT (1967). Renal neoplastia induced by combinations of dietary lead subacetate abd N-2-fluorenylacetamide. In: Renal Neoplasia. JS King (ed). Little, Brown & Co., Boston, MA, pp. 377-412.
16.
16. Hecht SS, Chen CHB, Nirota N, Ornat RM, Tso TC, and Hoffman D (1978). Tobacco-specific nitrosamines: Formation from nicotine in vitro and during tobacco curing and carcinogenicity in strain A mice.J. Natl. Cancer Inst.60: 819–825.
17.
17. Hemphill DD, Marienfeld CJ, Reddy RS, and Pierce JO (1974). Roadside lead contamination in the Missouri lead belt.Arch. Environ. Health28: 190–196.
18.
18. Herring HD (1972). Effect of nitrite and other factors on the physico-chemical characteristics and nitrosamine formation in bacon. Proceedings of the Meat Industry Research Conference.American Meat Institute Foundation, Chicago, pp. 47–60.
19.
19. Hinton DE, Heatfield BM, Lipsky MM, and Trump BF (1980). Animal model: Chemically induced renal tubular carcinoma in rats.Am. J. Pathol.101: 317–320.
20.
20. Hoffman DG, Rothkamp G, and Lin YY (1966). N-Nitroso compounds in the environment. Publ. No. 4, Int. Agency Res. Cancer, Lyon.
21.
21. Ivankovic S and Preussman R (1970). Transplazentare erzengung maligner tumorin nach oraler gabe von athylharnstoff und nitrit von ratten.Naturwissenschaften57: 460–465.
22.
22. Kerkvliet NI and Baecher-Steppan L (1982). Immunotoxicology studies on lead: Effects of exposure on tumor growth and cell-mediated tumor immunity after syngeneic or allogeneic stimulation.Immunopharmacology4: 213–214.
23.
23. Klein G and Klein E (1977). Immune surveillance against virus-induced tumors and nonrejectbility of spontaneous tumors. Contrasting consequences of host versus tumor evolution.Proc. Natl. Acad. Sci. U.S.A.74: 2121–1229.
24.
24. Kobayashi N and Okamoto T (1974). Effects of lead oxide on the induction of lung tumors in Syrian hamsters.J. Natl. Cancer Inst.52: 1605–1610.
25.
25. Koller LD (1980). Immunotoxicology of heavy metals.Int. J. Immunopharmacol.2: 269–279.
26.
26. Lijinsky W, Taylor HW, Snyder C, and Nettesheim P (1973). Malignant tumors of liver and lung in rats fed aminopyrine or heptamethyleneimine together with nitrite.Nature244: 174–178.
27.
27. Low H (1974). Nitroso compounds. Arch. Environ. Health29: 256.
28.
28. Magee PN (1971). Toxicity of nitrosamines: Their possible human health hazards.Food Cosmet. Toxicol.9: 491–503.
29.
29. Mao P and Molnar JJ (1967). The fine structure and histochemistry of lead-induced renal tumors in rats.Am. J. Pathol.50: 571–603.
30.
30. Mirvish SS (1971). Kinetics of nitrosamide formation from alkylureas, N-alkylurethans, and alkylguanidines: Possible implications for the etiology of human gastric cancer.J. Natl. Cancer Inst.46: 1183–1193.
31.
31. Moore MR and Meredith PA (1979). The carcinogenicity of lead.Arch. Toxicol.42: 87–94.
32.
32. Morgan JM, Harley NW, and Miller RE (1966). Neuropathy in chronic lead poisoning.Arch. Int. Med.118: 17–29.
33.
33. Neurath GB, Dunger M, Pein FG, Ambrosius D, and Schreiber O (1977). Primary and secondary amines in the human environment. Food Cosmet. Toxicol.15: 275.
34.
34. Nixon JE, Koller LD, and Exon JH (1979). Effect of methylmercury chloride on transplacental tumors induced by sodium nitrite and ethyl urea in rats.J. Natl. Cancer Inst.63: 1057–1063.
35.
35. Osske VG, Warzok R, and Schneider J (1972). Transplacental induction of tumors endogenously formed N-ethyl-N-nitrosourea in rats.Arch. Geschwulstforsch.40: 244–249.
36.
36. Sander J (1971). Untersuchungen uber die entstehung carcinogener nitrosoverbindungen im magen von versuchstieren und ihre bedeuting fur den Menschen.Arzneimittelforsch21: 1572–1580, 1707-1713, 2034-2039.
37.
37. Sander J, Burkle G, and Flohe L (1971). Untersuchungen in vitro uber die moglichkeit ciner bildung cancerogener nitrosamide in magen.Arzneimittelforsch21: 411–414.
38.
38. Sen NP, Miles WF, Donaldson B, Panalaks T, and Iyengar JR (1973). Formation of nitrosamines in a meat curing mixture.Nature245: 104–105.
39.
39. Sen NP, Seaman S, and Miles WF (1975). Dimethylnitrosamine and nitrosopyrrolidine in fumes produced during the frying of bacon.Food Comet. Toxicol.14: 167–171.
40.
40. Serofeontein WJ and De Villiers LS (1975). Druginduced biogenesis of nitrosamines.Res. Commun. Chem. Pathol. Pharmacol.12: 605–608.
41.
41. Shuval HI and Gruener N (1972). Epidemiological and toxicological aspects of nitrates and nitrites in the environment.Am. J. Public Health62: 1045–1051.
42.
42. Swenberg JA, Koestner A, LSWechsler IV, and Denlinger RH (1972). Quantitative aspects of transplacental tumor induction with ethylnitrosourea in rats.Cancer Res.32: 2656–2660.
43.
43. Tarr HLA and Sunderland PA (1940). Effectiveness of ice containing sodium nitrite for fish preservation.J. Fish. Res. Board. Can.5: 36–42.
44.
44. Van Esch GJ and Kroes R (1969). The induction of renal tumors by feeding basic lead acetate in mice and hamsters.Br. J. Cancer23: 765–771.
45.
45. Ziegfield RL (1964). Important uses of lead.Arch. Environ. Health8: 202–211.
46.
46. Zollinger HU (1953). Durch chronische bleivergiftung erzeugte neiren adenome und carcinome bie Ratten und ihre bezeihungen zu des entsprechender neubildungen des menschen.Virchows Arch. Pathol. Anat. Physiol.323: 694–710.
