Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4-Nitroquinoline 1-oxide (4NQO) is a model chemical carcinogen that has often been referred to as a UV mimetic agent. Previous studies have indicated that UV-induced pyrimidine dimers are repaired preferentially and strand-specifically in actively transcribing genes. In the current study we have examined the gene-specific and strand-specific repair of 4NQO in Chinese hamster ovary B-11 cells treated with 2.5 microM 4NQO. The methodology used for detecting adducts involved the treatment of DNA from 4NQO-exposed cells with uvrABC excinuclease, which incises DNA at adduct sites, followed by denaturing gel electrophoresis of DNA, Southern hybridization, and probing for the sequence of interest. We examined the active and inactive coding regions of the DHFR gene, the active adenine phosphoribosyltransferase gene, relatively inactive c-fos oncogene, and the mitochondrial genome for 4NQO adducts. Initial 4NQO adduct levels found in these genes varied from 1.10 to 1.52 adducts/10 kilobases. Little difference in repair was found between active coding and inactive regions of the DHFR gene, or between DHFR, adenine phosphoribosyltransferase, and c-fos genes, which are transcribed at different levels. Approximately 71% of 4NQO adducts were repaired within 24 h in all gene sequences examined. During this same time period, approximately 51% of adducts were repaired from the genome overall, as determined by comparing the removal of bound radiolabeled 4NQO to total DNA. The results indicate that 4NQO adducts, unlike UV light-induced cyclobutane pyrimidine dimers (UV dimers), are not preferentially repaired in transcriptionally active genes. However, there may be regions of the genome that are not repaired with the same efficiency as the specific genes examined here. In addition, little to no difference was observed in the repair of 4NQO adducts in the transcribed and nontranscribed strands of the DHFR gene, a finding which is also in contrast to results with UV dimers. Interestingly, 4NQO adducts, unlike UV dimers, were removed from the mitochondrial genome, suggesting that repair of select lesions occurs in this organelle. Thus, there appear to be some differences in the repair pathways operating for 4NQO adducts and UV dimers, particularly with respect to gene- and strand-specific DNA repair.
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PMID:Gene- and strand-specific damage and repair in Chinese hamster ovary cells treated with 4-nitroquinoline 1-oxide. 163 32

This paper (1) presents an analysis of published data on the molecular nature of spontaneously arising and radiation-induced mutations in mammalian somatic cell systems and (2) examines whether the molecular nature and mechanisms of origin of radiation-induced mutations, in mammalian in vivo and in vitro systems, as currently understood, are consistent with expectations based on the biophysical and microdosimetric properties of ionizing radiation. Depending on the test system (CHO cells, human T lymphocytes and human lymphoid cell line TK6), 80-97% of spontaneous HPRT mutations show normal Southern patterns; the remainder is due to gross changes, predominantly partial (intragenic) deletions. Total gene deletions at the HPRT locus are rare except in the TK6 cell line. At the APRT locus in CHO cells, 80-97% of spontaneous mutations are due to base-pair changes, the remainder being, mostly, partial deletions. The latter can extend upstream in the 5' direction but not beyond the APRT gene in the 3' direction. At the human HLA-A locus (T lymphocytes), the percentage of mutations with normal Southern patterns is lower than that for HPRT, and in the range of 50-60%. At the HLA-A locus, mitotic recombination contributes substantially to the mutation spectrum (approximately 30% of mutations recovered) and this is likely to be true of the TK locus in the TK6 cell line as well. With a few exceptions, most of the radiation-induced mutations show altered Southern patterns and are consistent with their being deletions and/or other gross changes (HPRT, 70-90% (CHO); 50-85% (TK6); 50-75% (T lymphocytes); TK, 60-80% (TK6); HLA-A, 80% (T lymphocytes); DHFR, 100% (CHO]. The exceptions are APRT mutations in CHO cells (16-20% of mutants with deletions or other changes) and HPRT mutations in T lymphocytes from A-bomb survivors (15-25%); the latter finding is consistent with the occurrence of in vivo selection against HPRT mutant cells. In cases of HPRT intragenic deletions analyzed (CHO cells and V79 Chinese hamster cells), there is evidence for a non-random distribution of breakpoints. The spontaneous mutation frequencies vary widely, from about 0.04/10(6) cells (sickle cell mutations at the human HBB locus) to 30.8/10(6) cells (HLA-A mutations in T lymphocytes) and are dependent on the locus, the system employed and a number of other factors. Those for the other loci fall between these limits.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ionizing radiation and genetic risks. III. Nature of spontaneous and radiation-induced mutations in mammalian in vitro systems and mechanisms of induction of mutations by radiation. 202 1

A general approach for assaying the in vivo direction of replication for any DNA segment has been developed. This technique allows the scanning of genomic regions to detect bidirectional tail-to-tail replication, indicating the presence of a functional origin. By this criterion we identified the approximate positions of two origin sites downstream of the Chinese hamster DHFR gene. Further mapping revealed areas of head-to-head replication, signifying locations of replication termination and thus defining the landmarks of a complete animal cell replicon. Genetic proof for the existence of the DHFR origin was obtained by showing that this region serves as a bidirectional DNA synthesis initiation point following its integration into other sites in the genome by transfection. To show the general applicability of this methodology, we studied the APRT domain. Replication mapping together with the use of deletion mutants allowed the identification of an origin at a far-upstream locus.
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PMID:Mapping replication units in animal cells. 254 94