Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00249 (Mutagen)
 5,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Invertase formation in the yeast Saccharomyces cerevisiae is subject to repression by hexoses in the growth medium. Mutagen-induced (ethyl methanesulfonate or N-methyl-N-nitro-nitrosoguanidine) invertase hyperproducer mutants have been derived from the SUC3 MAL3 strain EK-6B by selecting for their ability to grow on media containing the sugar raffinose plus 2-deoxy-D-glucose (2DG). Raffinose like sucrose is a betta-fructoside which can be hydrolyzed by yeast invertase (beta-fructoside which can be hydrolyzed by yeast invertase (beta-fructofuranoside fructohydrolase). These mutants, designated dgr, produce higher levels of invertase (pi-glucosidase levels are also elevated but to a lesser extent) under conditions normally repressing invertase biosynthesis in the parent. Invertases of mutants dgr2 and dgr3 are indistinguishable from that of EK-6B with respect to their Km's for sucrose and thermal labilities. Genetic studies revealed that dgr2 and dgr3 are recessive and unlinked to the SUC3 gene.
Mol Gen Genet 1978 Sep 08
PMID:Genetic control of invertase formation in Saccharomyces cerevisiae. II. Isolation and characterization of mutants conferring invertase hyperproduction in strain EK-6B carrying the SUC3 gene. 36 57

Selection for defective reversion induction, after UV treatment of E. coli K 12, yielded uvm mutants. These mutants exhibited highly reduced or no UV mutability for all loci tested although they were moderately and normally mutable by X-rays and EMS, respectively. Uvm mutations confer only a slight sensitivity to killing by UV and X-rays and no clear sensitivity to the lethal effect of HN2, EMS or MMS. Growth and viability of untreated uvm cells were normal. The properties of uvm mutants are discussed in relation to those of other relevant mutant types and to some actual problems of induced mutagenesis.
Mol Gen Genet 1978 Sep 20
PMID:Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. I. Isolation of uvm mutants and their phenotypical characterization in DNA repair and mutagenesis. 36 69

7-Methylbenz(a)anthracene (7-MBA) and its 5,6-oxide and trans-5,6- and trans-8,9-dihydrodiol were tested for carcinogenic activity in a system in which mouse lung tissue was incubated in the presence of a test compound for 1 h and then implanted into isologous mice. All four compounds gave small yields of adenomas and in addition the 5,6-oxide gave two carcinomas.
Cancer Lett 1977 Sep
PMID:The activity of 7-methylbenz(a)anthracene metabolites in an in vitro-in vivo carcinogenicity test using mouse lung tissue. 40 82

Proteins cross-linked to DNA after nitrogen mustard (HN2) treatment of cells or isolated nuclei were purified in CsCl gradients. The protein-DNA cross-links could be cleaved by incubation in dilute acid and could be stabilized by alkali pretreatment. These results indicate that proteins cross-linked to DNA by HN2 are bound to alkylated purines. Analysis of the DNA-bound proteins on NaDodSO4-polyacrylamide gels showed that primarily large nonhistone proteins are cross-linked to DNA in cells treated with HN2. Very little if any histone is cross-linked to the DNA. Comparison of DNA bound proteins from HN2-treated cells and HN2-treated nuclei showed that in general the same proteins are linked to DNA in both cases, but some qualitative and quantitative differences exist.
Biochemistry 1978 Sep 19
PMID:Characterization of DNA-protein cross-links formed by treatment of L1210 cells and nuclei with bis(2-chloroethyl)methylamine (nitrogen mustard). 56 84

The cytogenetic effects of intraperitoneally (i.p.) and subcutaneously (s.c.) administered nitrogen mustard (HN2) and cytosine arabinoside (ara-C) on bone-marrow and ascites tumour cells of mice were studied. Ehrlich ascites tumour-bearing mice were treated with the mutagens, and cytological preparations were made from ascites tumour and bone-marrow cells of the same animal. The following parameters were investigated: frequencies of mitotic and chromosomal aberrations, time of aberration maxima and aberration spectra. HN2 (0.68 mg/kg b.w.), when given i.p., induced in ascites tumour cells a strong inhibition of mitotic frequency and very high aberration rates, whereas in bone marrow no aberrant chromosomes were observed. On the other hand, after s.c. administration, the same dose induced more aberrant metaphases in bone marrow than in tumour cells. Ara-C (315 mg/kg b.w.) resulted, after s.c. administration, in higher aberration frequencies both in ascites and bone-marrow cells compared with i.p. treatment. All ascites tumour cells showed higher aberration requencies than bone-marrow cells. In bone marrow the aberration maximum occurred as soon as 6 h after treatment. Furthermore, clear differences with respect ot the types of aberration found in the two systems were evident. The differences caused by the different modes of administration in two different types of cell are discussed in terms of metabolic inactivation and differences of the two tissues with respect to karyotype, cell cycle time and repair capacity.
Mutat Res 1978 Sep
PMID:The effect of the mode of administration of nitrogen mustard and cytosine arabinoside on the production of chromosomal aberrations in mouse bone marrow and ascites tumour cells. 71 78

Immediate and delayed effects of nitrogen mustard (HN2) (0.1 mg/kg/day for 4 days) on the growth and cell proliferation patterns of the 3-methylcholanthrene-induced autogenous rat sarcoma were studied. Tumor cells were labeled continuously with 0.5 muCi tritiated thymidine/g for 24 hours. The labeling index fell from 36.4 to 14.0% and the mitotic index from 0.88 to 0.67% after two treatments with HN2. At that time, tumor growth stopped and remained arrested during HN2 administration. After four injections of HN2, the labeling index was reduced further to 0.73% and the mitotic index to 0.36%. After the drug was withdrawn, tumor growth resumed at the pretreatment rate, even though the labeling index on day 3 was only 15.5% (or 40% of the control). The percent labeled mitosis curves and DNA contents, before and 4 days after HN2 was given, were similar. It was concluded that a subpopulation of cells of predominantly short intermitotic times caused tumor growth before and after drug treatment.
J Natl Cancer Inst 1975 Sep
PMID:Growth and regrowth of an autogenous rat sarcoma: effects of nitrogen mustard. 115 48

Osteoblasts, members of the marrow stromal cellular network, may play an active role in the hemopoietic microenvironment as well as in bone remodeling. In this study, we examined the extent to which marrow-derived osteogenic cells (MBA-15) possess various stromal functions. This marrow stromal-derived cell line was shown by us to exhibit osteoblastic characteristics in culture and to form bone in vivo. These cells are shown here to constitutively produce and secrete cytokines identified as M-CSF, GM-CSF, and IL-6. MBA-15 cells modulate growth of normal and malignant myeloid and lymphoid cells as well as leukemia cell lines in vitro. Cell-cell interactions were studied in co-cultures with adherent MBA-15 cells and the target hemopoietic cells. Growth inhibition effects, observed under various experimental conditions, can be attributed to the presence of different soluble and membrane-bound inhibitory activities produced by MBA-15 cells. Thus, MBA-15 cells spontaneously produce both stimulators and inhibitors that can affect myeloid and lymphoid cell growth. Marrow osteogenic cells may therefore participate in the stromal regulation of hemopoiesis.
Calcif Tissue Int 1992 Sep
PMID:Hemopoietic functions of marrow-derived osteogenic cells. 142 64

Stromal cells of bone marrow origin produce a variety of known cytokines and some factors exhibiting apparently new biological activities. Several of these were identified by the study of cell to cell interactions and were not found in detectable amounts in media conditioned by the cells. We describe here a culture system that enables the release of stromal cytokines into medium free of any added proteins and supplemented with peptides from casein hydrolysate (0.1%). The absence of serum proteins allows extensive concentration and monitoring of activities that are otherwise undetectable. Stromal cells of the MBA-2.1 clonal cell line were seeded in a stationary bed reactor packed with a carrier of non-woven fabric matrix. After a proliferation phase with serum containing medium, the cells were maintained for over 10 months in protein-free medium. Throughout this extended incubation in the absence of serum or serum replacing proteins, stromal cells retained their viability and continuously released transforming growth factor-beta (TGF-beta), macrophage-colony stimulating factor (M-CSF) and restrictin-P, a cytotoxic factor that specifically arrested the growth of plasmacytoma cells. In addition, interleukin-6 (IL-6) was first undetectable, and later in culture its titer reached a maximum of 180,000 international units (IU)/ml. Concomitantly, the production of restrictin-P diminished and reached its lowest levels at the end of 10 months. The results may imply a possible causal relationship between the expression of IL-6 and restrictin-P, since no similarly significant changes were observed in the titers of M-CSF and TGF-beta. This novel bioreactor system may be adaptable for efficient production of different cytokines under absolute serum-free conditions.
Int J Cell Cloning 1992 Sep
PMID:Dynamic changes in cytokine secretion by stromal cells during prolonged maintenance under protein-free conditions. 145 17

Levels of unscheduled DNA synthesis (UDS) of peripheral blood lymphocytes were measured by liquid scintigraphy in 23 patients with hepatocellular carcinoma (HCC), 42 first-degree relatives of HCC, 17 carriers of HBsAg, and 47 controls in order to evaluate the effects of HN2.HCl on the damage and repair of cell DNA, the effects of genetic susceptibility on the development of HCC, and the relationship between genetic susceptibility and hepatitis B virus (HBV) infection. The results were: 1. UDSs were significantly increased in the peripheral blood lymphocytes from patients with HCC and their first-degree relatives, and higher than those of the controls (P less than 0.005). 2. UDS in HBsAg carriers was significantly higher than that of the controls (P less than 0.05), 3. The difference of UDS was also remarkable between the HBsAg-negative patients with HCC and their first-degree relatives and the controls (P less than 0.01). These results suggest that the development of HCC might be due to the combined effects of environmental factors and genetic susceptibility. As an environmental factor, HBV infection might play role in hepato-carcinogenesis in individuals with or without a genetic background.
Zhonghua Zhong Liu Za Zhi 1991 Sep
PMID:[Unscheduled DNA synthesis of peripheral blood lymphocytes in pedigrees of hepatocellular carcinoma patients]. 166 15

The inducibility of the mammalian O6-methylguanine-DNA methyltransferase (MGMT) gene encoding the MGMT protein (EC 2.1.1.63) responsible for removal of the procarcinogenic and promutagenic lesion O6-alkylguanine from DNA was examined by an analysis of transcription of the MGMT gene following exposure of repair-competent (Mex+) and repair-deficient (Mex-) cells to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). While human and rodent Mex- cells (CHO-9, V79, HeLa MR) showed no detectable MGMT mRNA despite the presence of the gene in their genome, the amount of it in several Mex+ lines (NIH 3T3, HeLa S3, HepG2) paralleled their MGMT activity. However, none of these cell lines showed an increase in the MGMT mRNA level after treatment with various concentrations of MNNG. In contrast, MNNG-treated rat hepatoma cells, H4IIE and FTO-2B, both Mex+, had three- to fivefold more MGMT mRNA than the corresponding untreated controls as measured 12 to 72 h after alkylation. N-Methyl-N-nitrosourea, methyl methanesulfonate, N-hydroxyethyl-N-chloroethylnitrosourea, UV light, and X rays caused a similar accumulation of MGMT mRNA in rat hepatoma cells. Studies with inhibitors of RNA and protein synthesis indicate that the induced increase in the amount of MGMT mRNA was due to enhanced transcription of the gene. Furthermore, they revealed the turnover of the MGMT mRNA to be relatively low (half-life, greater than 7 h). Mutagen-induced increase of transcription of MGMT mRNA in H4IIE cells was accompanied by elevation of MGMT repair activity and resulted in reduction of mutation frequency after a challenge dose of MNNG. Although induction of MGMT mRNA transcription has been observed in two rodent hepatoma cell lines so far, this appears to be the first demonstration of inducibility of a mammalian gene encoding a clearly define DNA repair function. The transcription activation of the MGMT gene protects cells from the mutagenic effects of methylating agents.
Mol Cell Biol 1991 Sep
PMID:Inducibility of the DNA repair gene encoding O6-methylguanine-DNA methyltransferase in mammalian cells by DNA-damaging treatments. 187 45


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