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1.
J Toxicol Sci ; 41(1): 91-104, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26763396

ABSTRACT

We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.


Subject(s)
Anthraquinones/administration & dosage , Anthraquinones/toxicity , Kidney/cytology , M Phase Cell Cycle Checkpoints/drug effects , Nitrofurantoin/administration & dosage , Nitrofurantoin/toxicity , Propane/analogs & derivatives , Animals , Body Weight/drug effects , Carboxin/administration & dosage , Carboxin/toxicity , Cell Proliferation/drug effects , Chlorohydrins/administration & dosage , Chlorohydrins/toxicity , Histones/metabolism , Kidney/drug effects , Male , Organ Size/drug effects , Propane/administration & dosage , Propane/toxicity , Rats, Inbred F344 , Time Factors , Triamterene/administration & dosage , Triamterene/toxicity , Ubiquitins/metabolism
2.
Biosci Biotechnol Biochem ; 75(1): 181-4, 2011.
Article in English | MEDLINE | ID: mdl-21228470

ABSTRACT

Five carboxin-resistant mutants from Aspergillus oryzae were characterized by the sensitivities of their mycelial growth and succinate dehydrogenase (SDH) activity to carboxin and three related fungicides. Despite a significant resistance to carboxin, exhibited by all the mutants, their patterns of sensitivity to the other fungicides was distinct. This provides clues to the molecular interaction between SDH and these fungicides.


Subject(s)
Aspergillus oryzae/drug effects , Aspergillus oryzae/genetics , Carboxin/toxicity , Drug Resistance, Fungal/genetics , Fungicides, Industrial/toxicity , Mutation , Aspergillus oryzae/enzymology , Mycelium/drug effects , Mycelium/enzymology , Mycelium/genetics , Succinate Dehydrogenase/metabolism
3.
J Agric Food Chem ; 52(20): 6228-32, 2004 Oct 06.
Article in English | MEDLINE | ID: mdl-15453691

ABSTRACT

Sunlight exposure of aqueous suspensions of carboxin (1) causes its phototransformation to sulfoxide 2 and minor components. Similar effects are observed in the presence of humic acid or nitrate or at different pH values. Photoproducts 2-9 were isolated by chromatographic techniques and/or identified by spectroscopic means. Carboxin 1 and its main photoproduct sulfoxide 2 were tested to evaluate acute toxicity to primary consumers typical of the aquatic environment: the rotifer Brachionus calyciflorus and two crustaceans, Daphnia magna and Thamnocephalus platyurus. Chronic tests comprised a producer, the alga Pseudokirchneriella subcapitata, and a consumer, the crustacean Ceriodaphnia dubia.


Subject(s)
Carboxin/chemistry , Carboxin/toxicity , Fungicides, Industrial/chemistry , Fungicides, Industrial/toxicity , Sulfoxides/toxicity , Water/chemistry , Animals , Crustacea/drug effects , Eukaryota/drug effects , Photochemistry , Rotifera/drug effects
5.
Proc Natl Acad Sci U S A ; 88(15): 6740-4, 1991 Aug 01.
Article in English | MEDLINE | ID: mdl-1713689

ABSTRACT

Oxathiin carboxanilide (OC), NSC 615985, a compound originally synthesized as a potential fungicide, was demonstrated to be highly active in preventing human immunodeficiency virus (HIV)-induced cell killing and in inhibiting HIV reproduction. Virus-infected CD4+ lymphocytes were completely protected by 0.5 microM OC, whereas no toxicity was observed at concentrations below 50 microM OC. Production of infectious virus, viral p24 antigen, and virion reverse transcriptase were reduced by OC at concentrations that prevented viral cell killing. A variety of CD4+ T-cell lines were protected by OC from HIV cytopathicity, and OC inhibited two distinct strains of HIV-1. However, HIV-2 infections were unaffected by OC. OC had no direct effect on virions of HIV or on the enzymatic activities of HIV reverse transcriptase or HIV protease. Time-limited treatments of cells with OC before, during, or after exposure of cells to virus failed to protect cells from the eventual cytopathic effects of HIV, and OC failed to inhibit the production of virus from cells in which infection was established or from chronically infected cells. We conclude that the highly active OC has a reversible effect on some early stage of HIV-1 reproduction and cytopathicity. Pilot in vivo experiments showed that circulating concentrations of OC exceeding 1 microM could be achieved and sustained in hamsters for at least a week with no remarkable toxicological sequelae. OC represents a new class of anti-HIV agents that are promising candidates for drug development.


Subject(s)
Antiviral Agents/pharmacology , Carboxin/analogs & derivatives , HIV-1/physiology , Virus Replication/drug effects , Animals , CD4 Antigens/analysis , Carboxin/blood , Carboxin/pharmacology , Carboxin/toxicity , Cell Line , Cricetinae , Drug Evaluation, Preclinical , HIV Protease Inhibitors , HIV-1/drug effects , HIV-1/enzymology , Humans , Reverse Transcriptase Inhibitors
6.
Environ Mol Mutagen ; 12(2): 235-42, 1988.
Article in English | MEDLINE | ID: mdl-3409877

ABSTRACT

The genotoxic effects of five pesticides (benomyl, 2,4-D, dimecron, monocrotophos, and vitavax) were evaluated in the rat bone marrow cytogenetic assay. The spectrum of aberrations observed included chromatid breaks, chromatid fragments, ring chromosomes, dicentric chromosomes, and chromosome fragments. It was observed that 2,4-D, dimecron, and vitavax were clastogenic, but the results obtained with benomyl and monocrotophos were equivocal.


Subject(s)
Anilides/toxicity , Carboxin/toxicity , Chromosome Aberrations , Pesticides/toxicity , 2,4-Dichlorophenoxyacetic Acid/toxicity , Animals , Benomyl/toxicity , Dose-Response Relationship, Drug , Monocrotophos/toxicity , Phosphamidon/toxicity , Rats
7.
Arch Exp Veterinarmed ; 34(3): 383-8, 1980.
Article in German | MEDLINE | ID: mdl-6159863

ABSTRACT

Acute oral toxicity to rat of phenyl-mercury acetate (with 44 mg/kg on males and between 54 mg/kg and 77 mg/kg on females several tests) was found to be almost identical with that of methyl-mercury toluenesulphamide (59 mg/kg on males, 54 mg/kg on females). Japanese quail, on the other hand, proved to much more sensitive to the methyl compounds, the significant difference being 25 mg/kg of methyl-mercury toluenesulphamide against 71 kg/kg of phenyl-mercury acetate. Coergistic action of combinations of phenyl-mercury acetate with HCB, Lindan, and Carboxin on female rats generally was poor. No deviation was established from additive action by a recently proposed method of evaluation. Conventional evaluation by means of an association factor (V) gave an antagonistic effect for the combination with Lindan (V = 0.54) and a potentiative effect for the combination with Carboxin (V = 1.70).


Subject(s)
Fungicides, Industrial/toxicity , Methylmercury Compounds/toxicity , Phenylmercuric Acetate/toxicity , Phenylmercury Compounds/toxicity , Animals , Carboxin/toxicity , Coturnix , Diet , Drug Interactions , Female , Hexachlorocyclohexane/toxicity , Lethal Dose 50 , Male , Rats , Sex Factors , Species Specificity
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