| Autor: |
Lina, Ben A. R., Woutersen, Ruud A., Bruijntjes, Joost P., Van Benthem, Jan, Van Den Berg, Jolanda A. H., Monbaliu, Johan, Thoolen, Bob J. J. M., Beems, Rudolf B., Van Kreijl, Coen F. |
| Předmět: |
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| Zdroj: |
Toxicologic Pathology; Mar/Apr2004, Vol. 32 Issue 2, p192-201, 10p, 5 Charts |
| Abstrakt: |
As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa -/- mice and the double knockout Xpa -/- .p53 +/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups of 15 male and 15 female Xpa -/- mice, Xpa -/- .p53 +/- mice and WT mice for 39 weeks. The model compounds investigated were haloperidol, reserpine (nongenotoxic rodent carcinogens, putative human noncarcinogens), phenacetin (genotoxic rodent carcinogen, suspected human carcinogen), and D -mannitol (noncarcinogen in rodents and humans). The test compounds were administered as admixture to rodent diet at levels up to 25 mg/kg diet for haloperidol, 7.5 mg/kg diet for reserpine, 0.75% for phenacetin, and 10% for D -mannitol. These levels included the maximum tolerable dose (MTD). Survival was not affected with any of the test compounds. Haloperidol, reserpine and D -mannitol were negative in the carcinogenicity assay with Xpa -/- and Xpa -/- .p53 +/- mice, showing low and comparable tumor incidences in controls and high-dose animals. The results obtained with phenacetin may be designated equivocal in Xpa -/- .p53 +/- mice, based on the occurrence of a single rare tumor in the target organ (kidney) accompanied by a low incidence of hyperplastic renal lesions and a high incidence of karyomegaly. These results are in agreement with the currently known carcinogenic potential of the 4 test compounds in humans. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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