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Defects in the xeroderma pigmentosum complementation group A-correcting (XPA) gene, which encodes a component of the nucleotide excision repair (NER) pathway, are associated with the cancer-prone human disease xeroderma pigmentosum. We previously generated mice lacking the XPA gene, which develop normally but are highly sensitive to ultraviolet-B and(More)
Phosphorylation is important for p53 protein stabilization and activation after DNA damage. Serine 389 of p53 is specifically phosphorylated after UV irradiation, whereas gamma radiation activates p53 through a different pathway. To study the in vivo significance of p53 phosphorylation at serine 389, we generated a physiological mouse model in which p53(More)
DNA repair deficient Xpa-/- and Xpa-/-/p53+/- knock-out mice in a C57BL/6 genetic background, referred to as respectively the XPA and XPA/p53 model, were investigated in the international collaborative research program coordinated by International Life Sciences Institute (ILSI)/Health and Environmental Science Institute. From the selected list of 21 ILSI(More)
The acute toxicity of a number of chlorinated benzenes, ranging from monosubstituted to pentasubstituted benzenes, was studied in rats. Toxic effects on the liver, the kidneys, and the thyroid were monitored after a single ip administration of 1, 2, or 4 mmol/kg monochlorobenzene (MCB), 1,2-dichlorobenzene (1,2-DICB), 1,4-dichlorobenzene (1,4-DICB),(More)
The effects of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were studied in DNA repair deficient XPA(-/-) mice. The nullizygous XPA-knockout mice, which lack a functional nucleotide excision repair (NER) pathway, were exposed to dietary concentrations ranging from 10 to 200 p.p.m. The results show that PhIP is extremely toxic to(More)
Patients carrying mutations in the XPB helicase subunit of the basal transcription and nucleotide excision repair (NER) factor TFIIH display the combined cancer and developmental-progeroid disorder xeroderma pigmentosum/Cockayne syndrome (XPCS). Due to the dual transcription repair role of XPB and the absence of animal models, the underlying molecular(More)
Trichothiodystrophy (TTD) patients with a mutation in the XPD gene of nucleotide excision repair (NER) have a short life span and show various features of premature aging, thereby linking DNA damage to the aging process. Xpd(TTD) mutant mice share many features with TTD patients, including a shorter life span, accompanied by a segmental progeroid phenotype.(More)
At present (putative) human carcinogens are identified via epidemiological studies and testing using the chronic 2-yr rodent bioassay. Both methods have severe limitations in that they are slow, insensitive, expensive, and are also hampered by many uncertainties. The development of methods to modify specific genes in the mammalian genome has provided(More)
Vinyl acetate was evaluated for chronic toxicity and oncogenicity in male and female rats and mice in a 104-week study. Target concentrations were 0, 50, 200, and 600 ppm. The study included interim terminations at approximately 53 and 83 weeks and a group whose exposure was terminated at 70 weeks and allowed a 15-week recovery period. Over the course of(More)
To study the role of particle size of benzo(a)pyrene (BP) in the induction of respiratory tract tumours, goups of hamsters were given 52 weekly intratracheal instillation of fine (77% less than 5.2 micron; 3% less than 1.3 micron) or coarse (77 less than 42 micron; 0% less than 10 micron) BP particles suspended in gelatin-0.9% NaCl solution. Both the fine(More)