Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Field studies suggest that recent epizootics of hepatic neoplasms in some feral fish populations are associated with polycyclic aromatic hydrocarbon (PAH) exposure, but attempts to induce liver tumors in these species under laboratory conditions have been unsuccessful. Several studies have shown hepatic neoplasma to be inducible in laboratory fish species following PAH exposure at the free-swimming life stage. However, neither the susceptibility of the fish embryonic life stage to tumor induction by PAHs nor the potential of these carcinogens to induce oncogenic point mutations analogous to those reported in feral fish hepatic tumors have been clearly established. To address this, rainbow trout embryos were exposed by passive water uptake to 7,12-dimethylbenz[a]anthracene (DMBA), a potent model PAH in many mammalian tumor protocols. DMBA was rapidly absorbed by trout eggs and metabolized. The major non-polar metabolites identified were 12-hydroxymethyl-7-methylbenz[a]anthracene and 3,4-dihydroxy-3,4-dihydro-DMBA, whereas approximately 25% of the water soluble metabolites were identified as glucuronides by beta-glucuronidase treatment. Embryonic DNA adduction increased with time of DMBA exposure (2.2 +/- 0.3 pmol DMBA-equivalents/mg DNA at 24 h). Liver tumor incidence nine months after DMBA treatment was found to increase with DMBA concentration and exposure period (3.8% at 1 p.p.m./2 h; 23% at 5 p.p.m./2 h; 85% at 5 p.p.m./24 h). Stomach adenomas and nephroblastomas also were observed at low incidence in the DMBA-treated trout. Among 11 hepatic tumors examined, nine carried Ki-ras alleles with activating point mutations in codon 12 (4/11 GGA-->AGA; 4/11 GGA-->GTA) or codon 61 (1/11 CAG-->CTG). This spectrum differs substantially from those reported for DMBA-initiated mouse skin papillomas or hepatic tumors. These results may have important environmental implications because they suggest that even a brief exposure to PAHs during a sensitive stage of development may adversely affect some fish populations. They also indicate considerable variation in DMBA ras gene mutations among species and target organs.
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PMID:Carcinogenicity, metabolism and Ki-ras proto-oncogene activation by 7,12-dimethylbenz[a]anthracene in rainbow trout embryos. 847 26

The transient expression of three novel plant amber suppressors derived from a cloned Nicotiana tRNA(Ser)(CGA), an Arabidopsis intron-containing tRNA(Tyr)(GTA) and an Arabidopsis intron-containing tRNA(Met)(CAT) gene, respectively, was studied in a homologous plant system that utilized the Agro bacterium-mediated gene transfer to Arabidopsis hypocotyl explants. This versatile system allows the detection of beta-glucuronidase (GUS) activity by histochemical and enzymatic analyses. The activity of the suppressors was demonstrated by the ability to suppress a premature amber codon in a modified GUS gene. Co-transformation of Arabidopsis hypocotyls with the amber suppressor tRNA(Ser) gene and the GUS reporter gene resulted in approximately 10% of the GUS activity found in the same tissue transformed solely with the functional control GUS gene. Amber suppressor tRNAs derived from intron-containing tRNA(Tyr) or tRNA(Met) genes were functional in vivo only after some additional gene manipulations. The G3:C70 base pair in the acceptor stem of tRNA(Met)(CUA) had to be converted to a G3:U70 base pair, which is the major determinant for alanine tRNA identity. The inability of amber suppressor tRNA(Tyr) to show any activity in vivo predominantly results from a distorted intron secondary structure of the corresponding pre-tRNA that could be cured by a single nucleotide exchange in the intervening sequence. The improved amber suppressors tRNA(Tyr) and tRNA(Met) were subsequently employed for studying various aspects of the plant-specific mechanism of pre-tRNA splicing as well as for demonstrating the influence of intron-dependent base modifications on suppressor activity.
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PMID:Translational nonsense codon suppression as indicator for functional pre-tRNA splicing in transformed Arabidopsis hypocotyl-derived calli. 1258 39