Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethylene oxide (EtO)-induced mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene were characterized in 28 independently derived 6-thioguanine-resistant human diploid fibroblast clones using polymerase chain reaction-based techniques and Southern blot analysis. Sequence analysis revealed one single base pair deletion and 13 base substitutions, nine of which were transversions: five AT-->TA, three GC-->TA and one GC-->CG. Four mutants were found to have GC-->AT transitions. Seven of the point mutations caused splicing errors. Six occurred in splice site sequences and one created a new splice acceptor site 16 bp upstream of exon 9. Three splice mutations were localized at the same site in the splice donor sequence of intron 8. Fourteen mutants had large HPRT gene deletions. In seven mutants the entire HPRT gene was deleted. The remaining deletion mutants had a truncated HPRT gene, where one or several exons were lost. These results show that EtO induces many different kinds of HPRT mutations, among which as many as 50% are large deletions.
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PMID:Molecular analysis of ethylene oxide-induced mutations at the HPRT locus in human diploid fibroblasts. 768 88

A review of the epidemiological and mechanistic data on 1,3-butadiene indicates that this chemical is a human carcinogen for which the mouse is an appropriate model for assessing human cancer risk. Butadiene is carcinogenic at multiple organ sites in laboratory animals, including the induction of lymphomas in mice, while epidemiological studies have consistently found associations between occupational exposure to butadiene and increased mortality from lymphatic and hematopoietic cancers. Activated oncogenes and inactivated tumor suppressor genes in butadiene-induced tumors in mice are analogous to genetic alterations frequently observed in human cancers. Butadiene is metabolized to mutagenic and carcinogenic epoxides in all mammalian species studied, including humans. These metabolites form N7-alkylguanine adducts which have been detected in liver DNA of mice exposed to butadiene and in urine of exposed workers. Increases in hprt mutations were observed in lymphocytes from mice exposed to butadiene and in occupationally exposed humans. The mutational spectra for butadiene and its epoxide metabolites at the hprt locus in mouse lymphocytes are similar to the mutational spectrum of ethylene oxide; all of these chemicals exhibit a high percentage of frameshift mutations. Ethylene oxide, an alkylating agent that also forms an N7-alkylguanine adduct, was recently classified by the International Agency for Research on Cancer as a human carcinogen. Based on these data, we suggest that cancer induction by ethylene oxide and butadiene involve similar molecular mechanisms.
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PMID:Mechanistic data indicate that 1,3-butadiene is a human carcinogen. 785 43