Summary
The anti-inflammatory agent diftalone was administered in the diet to male and female BALB/c mice at 300-, 600-, and 1200-ppm dose levels for 80 weeks, starting at 8 weeks of age. The animals were kept under observation until 126–128 weeks of age, when the experiment was terminated. Diftalone treatment at the highest dose was hepatotoxic and induced hepatocellular tumors in females, angiomas of the liver in males, and angiosarcomas of the liver in male and female mice. The 300- and 600-ppm dose levels were not carcinogenic. The compound was not mutagenic for Salmonella typhimurium.
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References
Ames BN, McCann J, Yamasaki E (1975) Methods for detecting carcinogens and mutagens in the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 31:347–364
Dragani TA (1979) Analysis of tumor incidence in BALB/c mice used as controls in carcinogenicity experiments. Tumori 65:665–675
Farber E (1963) Ethionine carcinogenesis. Adv Cancer Res 7:383–474
IARC (1979) IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: Some halogenated hydrocarbons, Lyon, France, vol 20, pp 371–399
Leopold WR, Miller JA, Miller EC (1982) Comparison of some carcinogenic, mutagenic, mutagenic, and biochemical properties of S-vinylhomocysteine and ethionine. Cancer Res 42:4364–4374
Levin DE, Hollstein M, Christman MF, Schwiers EA, Ames BN (1982) A new Salmonella tester strain (TA 102) with A·T base pairs at the site of mutation detects oxidative mutagens. Proc Natl Acad Sci USA 79:7445–7449
Nickander R, McMahon FG, Ridolfo AS (1979) Nonsteroidal antiinflammatory agents. Ann Rev Pharmacol Toxicol 19:469–490
Ong T, Mukhtar M, Wolf CR, Zeiger E (1980) Differential effects of cytochrome P450-inducers on promutagen activation capabilities and enzymatic activities of S-9 from rat liver. Environ Pathol Toxicol 4:55–65
Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35:1–39
Peto R, Pike MC, Day NE, Gray RG, Lee PN, Parish S, Peto J, Richards S, Wahrendorf J (1980) Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments. IARC, Lyon, pp 311–426 (IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Suppl. 2, Long-term and short-term screening assays for carcinogens: A critical appraisal)
Schiatti P, Selva D, Arrigoni-Martelli E, Lerner LJ, Diena A, Sardi A, Maffii G (1974) Antiinflammatory activity and other pharmacological properties of phthalazino(2,3-b)phthalazine-5,12(7H,14H)-dione (Diftalone). Arzneimittelforsch 24:2003–2009
Sheldon WG, Greenman DL (1979) Spontaneous lesions in control BALB/c female mice. J Environ Pathol Toxicol 3:155–167
Strolin Benedetti M, Assandri A, Schelling J-L, Villani F (1977) Physiological disposition and plasma metabolites of a new antiinflammatory agent, diftalone, in rat, dog, monkey and man. Arzneimittelforsch 27:2364–2368
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Porta, G.D., Dragani, T.A., Barale, R. et al. Carcinogenic activity in mice of diftalone, an anti-inflammatory agent. J Cancer Res Clin Oncol 108, 308–311 (1984). https://doi.org/10.1007/BF00390463
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DOI: https://doi.org/10.1007/BF00390463