In:
Toxicologic Pathology, SAGE Publications, Vol. 32, No. 2 ( 2004-02), p. 192-201
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0192-6233
,
1533-1601
DOI:
10.1080/01926230490274344
Language:
English
Publisher:
SAGE Publications
Publication Date:
2004
detail.hit.zdb_id:
2056753-4
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