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© 1989 Oxford University Press

research-article

Comparison of three rat liver foci bioassays-incidence of preneoplastic foci initiated by diethylnitrosamine

D. Oesterle, U. Gerbracht 1, E. Deml, B. Schlatterer 2 and D. Eigenbrodt 1

GSF-Institute of Toxicology D-8042 Neuherberg
1Institute of Biochemistry and Endocrinology, University of Giessen D-6300 Giessen
2Umweltbundesamt D-1000 Berlin, FRG

Three rat liver foci bioassays have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic foci, and by the biochemical determination of alterations in enzyme activities of serum indicating hepatotoxicity. We studied the initiation/promotion schedules according to Oesterle and Deml (A), and according to Pereira (B, Broad Spectrum Protocol), and the initiation/selection protocol according to Tatematsu et al. (C), with diethyl nitrosamine (DEN), given as a single initiating dose of 10 and 30 mg/kg body wt respectively. With all schedules Sprague-Dawley rats, either females, 3 weeks old (A), or males, 6 weeks old (B, C) were used. For promotion polychiorinated biphenyls (A) or phenobarbital (B) were administered. Selection was performed with 2-acetylaminofluorene (C). The rats in schemes (B) and (C) underwent partial hepatectomy one day prior to initiation. The number and total area of foci deficient in adenoslne-5'-triphosphatase (ATPase) and positive in {gamma}-glutamyttranspeptidase (GGTase) was evaluated. In the complete schedule with 30mg of DEN in system (A) foci incidence exceeded that of the other systems by about 7-fold (ATPase) and 2-fold (G.GTase) respectively. The tower dose of DEN and all control experiments resulted In a respective lower foci yield. With scheme (C), but not with schemes (A) and (B), e.g. serum fructose-1.6-bisphosphatase and alkaline phosphatase were increased, suggesting liver cell damage. Thus tested with DEN, scheme (A) is most sensitive and causes a low impairment of animals' welfare.


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