Loss of one allele of the p53 gene in the lens epithelial tumor in transgenic mice suppresses apoptosis induced by a topoisomerase I inhibitor (CPT-11).
To examine whether CPT-11 can induce apoptosis in the mouse lens tumor, it was administered to pregnant alphaT3 mice, which developed epithelial tumors in the lens during the perinatal stage. Three different p53 genotypes were generated to analyze the influence of p53 status on tumor cells under chemotherapy. On day 16--17 of gestation, alphaT3 mice received an i.p. injection of CPT-11, and fetal lens tumors were examined 2 days later. Apoptosis in the tumors was observed in both a CPT-11 dose- and p53 gene copy-dependent manner. In addition, it was found that CPT-11 could also induce apoptosis via a p53-independent pathway.
Nakajima
Yasuo
Y
Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Yamadaoka 2-2 Suita, Osaka, Japan.
Nakamura
Takafumi
T
Enomoto
Takayuki
T
Murata
Yuji
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005134:Eye Neoplasms / Q000235:genetics / Q000473:pathology*; D005838:Genotype; D020287:In Situ Nick-End Labeling; D000077146:Irinotecan; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53; D000077146:Irinotecan; D002166:Camptothecin