Journal article
Assessment of Carcinogenicity of di(2-ethylhexyl) phthalate in a short-term assay using Xpa(-/-) and Xpa(-/-)/p53(+/-) mice
The potential of Xpa(-/-) and Xpa(-/-)/p53(+/-) mice for short-term carcinogenicity assays was evaluated with di(2-ethylhexyl)phthalate (DEHP). Groups of 15 male and female Xpa(-/-) mice, received diets containing 0, 1,500, 3, 000, or 6,000 ppm DEHP, and wild-type (WT) and Xpa(-/-)/p53(+/-) mice 0 or 6,000 ppm DEHP for 39 weeks.
Xpa(-/-), Xpa(-/-)/p53(+/-), and WT males, fed 2,500 ppm p-cresidine, served as a positive control. In all models, the survival was not altered by DEHP. Increased incidences of nonneoplastic lesions were recorded in testes and kidneys with no apparent difference between the models. The only liver tumors in all models were adenomas in males with no statistically significantly increased incidence.
For p-cresidine, the survival was decreased (p <0.05) only in transgenic models. Statistically significantly increased incidences of nonneoplastic lesions were recorded in the liver, urinary bladder, and nasal cavity in all models, and in kidneys in transgenic models. The only tumors with statistically significantly increased incidence were liver adenomas in transgenic models (XPA:1 vs 7; `XPA/p53': 0 vs 12; WT: 0 vs 5, p = 0.053) and urinary bladder carcinomas in XPA/p53 model (0 vs 7).
The negative carcinogenic response to DEHP and the positive response to p-cresidine support the expected sensitivity to genotoxic carcinogens in these transgenic models.
Language: | English |
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Publisher: | Sage Publications |
Year: | 2002 |
Pages: | 188-199 |
ISSN: | 15331601 and 01926233 |
Types: | Journal article |
DOI: | 10.1080/019262302753559524 |
ORCIDs: | Sørensen, Ilona Kryspin |
XPA carcinogenicity testing hepatocellular adenoma p-cresidine p53 tumor suppressor gene testicular atrophy xeroderma pigmentosum
Animals Body Weight DNA-Binding Proteins Diethylhexyl Phthalate Dose-Response Relationship, Drug Drinking Female Male Mice Mice, Inbred C57BL Neoplasms, Experimental RNA-Binding Proteins Tumor Suppressor Protein p53 Xeroderma Pigmentosum Group A Protein Xpa protein, mouse p-cresidine.