Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constitutional loss or inactivation of one copy of a tumor-suppressor gene, as exemplified by hereditary retinoblastoma, increases the propensity for malignancies by reducing the number of events necessary for the complete loss of the negative regulatory function. We developed a selectable mutation assay employing a human lymphoblastoid cell line (LCL) derived from a heterozygous carrier of 2,8-dihydroxyadenine urolithiasis, adenine phosphoribosyltransferase (APRT) deficiency, for dissecting the second step in loss-of-function mutations and for determining the potential of physical and chemical agents for producing such mutations. The mode of mutational events arising in the wild-type allele of the functionally heterozygous APRT gene resembled that reported for tumor-suppressor genes in malignancies in that mitotic non-disjunctions or recombinations as well as deletions prevailed. Ultraviolet light (UV) was much less efficient in inducing these types of mutations than ionizing radiation. A group of autosomal recessive cancer-prone diseases, including xeroderma pigmentosum (XP), has been characterized as being more susceptible to genomic insults, owing to some defects in DNA processing, such as replication, repair, or recombination. This increased genomic instability may accelerate the gain-of-function mutation at a proto-oncogene and/or the loss-of-function mutation at a tumor-suppressor gene. XP complementation group A (XP-A) LCLs were extremely sensitive to UV-mutagenesis at the hypoxanthine phosphoribosyltransferase (HPRT) locus even at equicytotoxic doses. Some unique mechanism may operate in UV-mutagenesis in XP-A. We have succeeded for the first time in rendering XP-A cells tumorigenic in athymic mice by applying multiple exposures to UV and subsequent treatment with TPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular bases for hereditary cancer-prone diseases. 129 55

The pharmacokinetics of [14C]terephthalic acid ([14C]TPA) were determined in Fischer-344 rats after intravenous and oral administration. After iv injection, the plasma concentration-time data were fitted using a three-compartment pharmacokinetic model. The average terminal half-life in three rats was 1.2 +/- 0.4 hr, and the average volume of distribution in the terminal phase was 1.3 +/- 0.3 liters/kg. Following administration by gavage, a longer terminal half-life was obtained, indicating that dissolution of [14C]TPA or absorption from the gut may be partially rate-limiting. Recovery of [14C]TPA in the urine following a bolus iv dose was 101 +/- 8%, indicating essentially complete urinary excretion of the compound. No evidence of metabolism of [14C]TPA was obtained by analysis of urine by high-performance liquid chromatography. [14C]TPA was transported to the fetus after administration of the compound to pregnant rats; however, the concentrations in fetal tissues were low relative to the corresponding maternal tissues. Neonatal rats exposed to 5% TPA in the diet of their dams did not develop calculi until the onset of self-feeding. These results demonstrate that TPA is rapidly excreted into urine after administration to rats, and that excretory mechanisms in the dam provide an effective mechanism of defense against TPA-induced urolithiasis in neonatal rats.
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PMID:Chemical urolithiasis. III. Pharmacokinetics and transplacental transport of terephthalic acid in Fischer-344 rats. 612 97