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Results for “Methylurea Compounds”

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PubMed2006

A comparative study on the protective effects of 17beta-estradiol, biochanin A and bisphenol A on mammary gland differentiation and tumorigenesis in rats.

Mammary tissue differentiation and tumorigenesis were studied in female rats following subcutaneous injection at 2, 4 and 6 days after birth with low or high doses of 17beta-estradiol (0.1 or 10 microg; E2), biochanin A (0.1 or 10 mg; BCA) or bisphenol A (0.1 or 10.0 mg; BPA). Half of the rats were killed on day 35 to analyze the terminal end bud (TEB), terminal duct (TD) and alveolar bud (AB) of the mammary tissue. The remaining rats were injected, ip, with a dose of 50 mg/kg of N-nitroso-N-methylurea (MNU) at 7 weeks of age and sacrificed 26 weeks later. The incidence and multiplicity of mammary tumors (MT) decreased among all three different treated groups, dose-dependently. However, the pattern of mammary gland differentiation varied. No significant difference was observed after E2 administration. TEB decreased dose-dependently in BCA treated groups and the number of TD and AB were suppressed significantly in BPA high dose group.

Animals↗

PubMed1981

[Genetic effects of N-nitroso-N-methylurea on Saccharomyces cerevisiae. II. Effect of radiosensitivity mutations on lethal and mutagenic effects].

Study of the lethal effect of NMU on radiosensitive strains rad2, rad54 and xrs2 of Saccharomyces cerevisiae has demonstrated that the mutations rad2 and rad54 increase the sensitivity of these strains to low doses of the mutagen. Mutations rad2, rad54 and xrs2 decreases the mutagenic effect of NMU. The study of nature of mutations induced by NMU in ade2 locus has shown that they are mainly the base substitutions. Mutations of radiosensitivity do not influence the nature of NMU-induced mutations in ade2 locus.

DNA Repair↗

PubMed1991

Trace analysis of nitrosated foodstuffs for nitrosamides.

An analytical procedure previously developed for the trace determination of nitrosamides was applied to a screening of nitrosated foodstuffs for nitrosoureas. Different types of foodstuffs were nitrosated both under chemical conditions using a high nitrite concentration, and under simulated gastric conditions. Methylating activity corresponding to N-nitroso-N-methylurea (MNU) was detected in most samples. Under chemical conditions, the yields spanned several orders of magnitude with processed fish and meat products being at the top, and plant products at the bottom of the scale. After nitrosation under simulated gastric conditions, the range of MNU activity was significantly smaller. No correlation exists between the yields determined under chemical and simulated gastric conditions.

Animals↗

PubMedDate not supplied

Study of the influence of certain antitumor preparations on the population of hematopoietic stem cells.

The influence of antitumor preparations 1,2-bisdiazoacetylethane (diazan) and N-nitroso-N-methylurea (NMU) on the inhibition of colony formation after sublethal irradiation and on migration after nonuniform irradiation of mice was investigated by methods of endogenous cloning of hematopoietic stem cells. It was shown that both preparations in the therapeutic doses used in experimental oncology (diazan 150 mg/kg, NMU 8 mg/kg) have no mitostatic effect on the hematopoietic stem cells, while NMU also does not influence their migration. Diazan somewhat stimulated the migration process.

Animals↗

PubMed1983

[Selective effect of p-aminobenzoic acid on mutagenesis: phenotypic analysis of the Arg+-revertants induced by N-nitroso-N-methylurea in the Escherichia coli K-12 AB1157 strain].

According to the phenotypic analysis of Arg+ revertants in Escherichia coli K-12 AB1157, the specific mutational changes in bacterial cells under the action of MNU were registered. True and suppressor mutations of four phenotypic groups were noted. The quantity of mutants induced depended upon the DNA and protein syntheses in bacterial cells. The sublethal concentration of para-aminobenzoic acid markedly (10-50 fold) reduced the rate of mutagenic induction and changed the quantity relations of mutants within phenotypic groups.

4-Aminobenzoic Acid↗

PubMed1996

Detection of methylating activity due to nitrosamide in some nitrosated Nigerian foodstuffs.

Popular vegetables, condiments and some Nigerian staple foods were evaluated for their relative methylating potential due to nitrosamide formation following nitrosation under standardized conditions. Methylating activity of nitrosated foodstuffs, expressed as N-nitroso-N-methylurea equivalents, was determined by gas chromatography-thermal energy analysis. In positive samples (detection limit 10 microgram/kg) methylating activity detected was in the range of 50-1200 microgram/kg, the highest activity being found in Telfairia occidentalis (ugwu). This value constitutes the highest amount ever detected for a fresh vegetable. The data suggest that some commonly consumed local foodstuffs might contribute to overall human burden of environmental carcinogens in Nigeria.

Carcinogens↗

PubMed1979

[Genetic effects of N-nitroso-N-methylurea on Saccharomyces cerevisiae yeasts. I. The influence of radiosensitivity mutations on lethal and recombinogenic effects].

Effect of mutations rad2 and rad54 in homozygous state on survival, mitotic segregation and crossing-over induced by NMU in yeast was studied. Mutation rad2 did not influence on these effects of NMU. The mutation rad54 increased sensitivity to the lethal effect, the frequencies of NMU-induced segregation and crossing-over were decreased in the strain rad54 rad54. The recombinogenic effect of NMU on yeast was lower than under the action of UV and gamma rays.

Crossing Over, Genetic↗

PubMed1977

Hepatocarcinogenic effects of N-nitroso-N-methylurea in guinea pigs.

Intragastric administration of N-nitroso-N-methylurea to strain 13 male guinea pigs, at a weekly dosage of 7.5 mg/kg for 15 weeks and then twice weekly for a subsequent 15 weeks, induced high toxicity, as evidenced by weight loss and mortality and a high incidence of malignant neoplasms, over a total observational period of 40 weeks. The neoplasms included hepatic angiosarcomas, cholangiocarcinomas, and generalized lymphoblastic lymphomas.

Adenoma, Bile Duct↗

PubMed1983

Viscometric detection of liver DNA fragmentation in rats treated with minimal doses of chemical carcinogens.

A new technique, using an oscillating viscometer capable of measuring changes of DNA reduced viscosity (eta red), has been used to detect DNA damage in liver of rats treated with various chemical carcinogens. In denaturing conditions (pH 12.5), the eta red of liver DNA from control rats increased slowly with time, reaching a maximum, (eta red)max, after 10 to 13 hr. Single i.p. doses of N-nitrosodimethylamine (0.07 mg/kg), N-nitrosodiethylamine (0.2 mg/kg), N-nitroso-N-methylurea (0.5 mg/kg), 1,2-dimethylhydrazine (0.06 mg/kg), procarbazine (1 mg/kg), methyl methanesulfonate (8 mg/kg), and N-diazoacetylglycine amide (3.7 mg/kg) induced a statistically significant reduction of the time (t95) required for eta red to reach its maximal value. A dose-dependent decrease of t95 was observed for dosages markedly lower than those found to be effective in eliciting DNA fragmentation by the use of alkaline elution or alkaline sucrose gradient sedimentation. 2-Acetylaminofluorene (12.5 mg/kg) and 4-nitroquinoline 1-oxide (10 mg/kg) caused a clear-cut increase of (eta red)max. 7,12-Dimethylbenz(a)anthracene (10 mg/kg) markedly prolonged t95. This viscometric assay of in vivo DNA damage allows a reliable assessment of DNA lesions induced by doses of chemical carcinogens sufficiently small not to produce significant alterations in the pharmacokinetic behavior of these compounds.

Animals↗

PubMed1975

[Response of flowering plant seedlings to the action of N-nitroso-N-methylurea].

The influence of N-nitroso-N-methylurea on seedlings of two species of plants--Cucurbita pepo L., Helianthus annuus L.--was investigated. NMU was added in agar-agar, on which seedlings were growing. 0.02% concentration of NMU was used. In addition to the delay in growth and appearance of necrotic regions, also local overgrowth of cotyledons of C. pepo and overgrowth of hypocotyl and the base of cotyledons of H. annuus were observed. A histological analysis has shown that these swellings arise due to two processes: pathological hypertrophy and proliferation.

Helianthus↗

PubMedDate not supplied

Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point mutations.

Each of nine mammary carcinomas induced by a single injection of nitroso-methylurea into 50-day-old Buf/N female rats, contained a transforming H-ras-1 gene. Molecular characterization of one of the genes revealed that the twelfth codon was GAA instead of GGA of the normal allele, encoding glutamic acid in place of glycine. These results indicate that chemical carcinogenesis represents an adequate model to study the role of transforming ras genes in human neoplasia.

Alleles↗

PubMed1990

Characterization of the effects of direct alkylators on in vitro immune responses.

Although their mechanism of degradation may differ, both the SN1 alkylators, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-nitroso-N-methylurea (MNU), and the SN2 alkylators, dimethyl sulfate (DMS) and methyl methanesulfonate (MMS), spontaneously decompose under aqueous conditions to the methyldiazonium ion or a direct methylating intermediate, respectively. Thus, these agents serve as useful probes to investigate the immunosuppressive potential of the putative primary reactive intermediate of dimethylnitrosamine (DMN) metabolism, the methyldiazonium ion. The effects of these direct alkylating agents on the in vitro immune response were characterized. Direct addition of both the SN1 and SN2 alkylators to naive B6C3F1 murine splenocytes produced a dose-dependent suppression of the in vitro antibody-forming cell (AFC) response to the T-dependent antigen, sheep erythrocytes (sRBC), T-independent antigen, dinitrophenyl (DNP)-Ficoll, and the polyclonal activator, lipopolysaccharide (LPS). The T-dependent and T-independent responses proved to be more sensitive than the polyclonal response to the effects of these compounds, except for MNNG in which all 3 antibody responses were equally affected. The suppression of the AFC response for all antigens was unaffected by the addition of 2-ME, and was observed at concentrations below those affecting viability, although at the highest concentrations an effect on viability was often observed. The addition of MNNG to the T-dependent AFC response at any time within the first 96 h produced a marked suppression, while the addition of DMS to cultures was only effective in suppressing the AFC response if added within the first 24 h. MNNG and DMS suppressed the proliferative responses to both B-cell (LPS) and T-cell (Concanavalin A; Con A) mitogens, as well as in the mixed lymphocyte response (MLR). In addition, a positive correlation between immunosuppression and DNA damage, as measured by single-strand breaks, was observed. Although these compounds produced suppression of in vitro immune responses, their profile of activity on immunocompetence and DNA damage was different from that associated with DMN and thus, the direct alkylators may not prove to be useful models to elucidate the mechanism of the DMN-induced immunosuppression.

Alkylating Agents↗

PubMed1986

Quantitative assessments of the cytotoxicity of bladder carcinogens towards cultured normal human uroepithelial cells.

Chemical carcinogens are known to exert cytotoxic effects on cells. The survival of cultured human uroepithelial cells (HUC) after exposure to several important classes of human and experimental animal bladder carcinogens has been quantitatively assessed in vitro using reduction in cell number and/or colony forming efficiency as the endpoint(s). Cells were treated with different carcinogens or various metabolites of a procarcinogen and the responses were analyzed with respect to the cell type used and to the donor source of the cells. The cytotoxic responses of HUC to the stable bladder procarcinogens tested [4-aminobiphenyl (ABP), 4-nitrobiphenyl, N-[4-(5-nitro-2-furyl)-2-thiazole]formamide and 2-amino-4-(5-nitro-2-furyl)thiazole] were dependent on both the concentration of chemical used and the duration of exposure. The survival of HUC after exposure to several metabolites of ABP differed. The N-hydroxylated derivatives of ABP (N-hydroxy-4-amino-biphenyl and N-hydroxy-4-acetylaminobiphenyl) were considerably more cytotoxic toward HUC than ABP or 4-acetylaminobiphenyl. The survival of HUC from different individuals after treatment with the direct acting carcinogen N-nitro-N-methylurea was very similar. In contrast, the survival of HUC from different donors varied considerably after treatment with the procarcinogen 3-methylcholanthrene which requires metabolic activation. However, significant heterogeneity in the survival of HUC from five donors after exposure to the human bladder procarcinogen ABP was not observed in this study. Cultures of normal human fibroblasts from four donors showed an unexpected heterogeneous response to the cytotoxic effects of ABP. These results demonstrate that many variables affect the cytotoxic response of normal cells to bladder carcinogens.

Aminobiphenyl Compounds↗

PubMed1976

[Structural derangements in deoxyribonucleoprotein complex damaged by N-nitroso-N-methylurea].

The effect of deoxyribonucleoproteid (DNP) solubilization under conditions of the ionic strength of the medium approaching the physiological one depended greatly after the treatment with a mutagen - N-nitroso-N-methylurea (NMU) on the NMU concentration. Apparently, for the change of DNA into a soluble state the critical number of groups in the DNA and protein should be modified. On the basis of the data obtained by circular dichroism and viscosimetry a conclusion was drawn that after the NMU treatment the DNP complex became soluble in the solvents with the ionic strength approaching the physiological one, chiefly as the result of labilization and dissociation of DNA-protein bonds.

Chemical Phenomena↗

PubMed1980

[Comparative effectiveness of different tests to determine the mutagenicity of certain factors in mammals. II. Frequency of anomalous sperm head in mice exposed to different factors].

The effect of a number of chemical and physical agents (cyclophosphamide (CTX) - 50, 100 and 300 mg/kg; N-nitroso-N-methylurea (NMU) - 50 mg/kg; N-nitrosomorpholine (NM) - 50 and 150 mg/kg; CdCl2 - 1, 2 and 4 mg/kg; ZnCl2 - 15 mg/kg; microwaves and gamma-rays 60Co on the frequency of abnormal sperm heads (ASH) in mouse F1 hybrids (C57BL X CBA) was studied. The agents possessing mutagenicity in the dominant lethal mutations (DLM) and bone marrow chromosome aberrations assay (CTX, NMU and gamma-rays) significantly increased the ASH frequency within 35 days after the treatment at maximum doses. CdCl2 inducing no mutagenic effect in the DLM test, increased the ASH frequency too. The increase in the ASH frequency all cases was accompanied by a reduction of the testicular weight and an increase in preimplantation losses and a reduction of the level of efficient matings when premeiotic germ cells were treated. This indicates that the occurrence of ASH may be due not only to the mutagenic but also cytolytic or/and cytotoxic effects of the compounds. The ASH test can be used for mutagenicity prescreening of different factors provided their doses are high enough.

Animals↗

PubMed1979

[Studies of the target cell problem in N-nitroso-N-methylurea induced leukemogenesis].

After i.p. application of 14C-nitrosomethylurea (NMU), mice were killed at different periods and the 14C-activity in various organs was determined by scintillation counting and by autoradiography. Contrary to expectations, bone marrow showed a significantly higher activity than the thymus, which is the supposed target-organ for the lymphatic leukemogenesis. The specificity was secured by examinations of the proliferation kinetics. The radioautographic results of bone marrow favorize the lymphatic cells as the target for NMU. The target-cell problem is discussed in respect to thymectomy examinations and recent results on nude mice. With high probability the thymus is not essential for lymphatic leukemogenesis.

Animals↗

PubMed2002

A field study to assess the degradation and transport of diuron and its metabolites in a calcareous soil.

An experimental plot has been established on a calcareous soil in southern England to investigate the fate and transport of diuron (N'-[3,4-dichlorophenyl]-N,N-dimethylurea), a commonly used phenylurea herbicide. An agricultural grade of diuron was applied to the soil surface at a rate of 6.7 kg/ha along with a potassium bromide conservative tracer applied at 200 kg/ha, in early January, 2001. Hand augured samples were taken at regular intervals over the next 50 days, with samples collected down to 54 cm. Porewaters were extracted from the soil cores by using high speed centrifugation and the supernatant fluids were retained for analysis by HPLC, for diuron and three of its metabolites, N'-[3,4-dichlorophenyl]-N,N-methylurea (DCPMU), N'-3,4-dichlorophenylurea (DCPU) and 3,4-dichloroaniline (DCA). The centrifuged soil was retained and then extracted with methanol prior to HPLC analysis for the same suite of phenylureas. A mass balance approach showed large variations in diuron distribution, but on average accounted for 104% of the diuron applied. Concentrations of diuron and its metabolites were roughly five times higher in the soil than in the soil porewaters. After 50 days, metabolites comprised 10% of the total diuron present in the porewater and 20% of the total diuron sorbed to the soil matrix. After 36 days, a large pulse of diuron and DCPMU appeared in the porewaters and soil matrix at a depth of 54 cm, travelling an average of 0.15 cm/day faster than Br. A preferential route for diuron transport is suggested. There is evidence to suggest that degradation occurs at depth as well as at the soil surface. Metabolites generally appear to move more slowly than the parent compound. All metabolites were encountered, but interpreting transport and degradation processes simultaneously proved beyond the scope of the study. Diuron was detected once in a shallow (5 m) observation well, situated on the experimental plot. High concentrations of diuron and metabolites were still present in the soil and soil solutions after 50 days and remain as a source of potential groundwater contamination.

Agriculture↗

PubMed1990

Inhibition by coffee of nitrosourea-mediated DNA damage in mice.

Oral administration of coffee at doses ranging from 150 mg to 1 g per kg body weight significantly decreased endogenously formed nitrosourea-mediated DNA damage in bone marrow as well as in colon epithelial cells in mice that had simultaneously received oral administration of methylurea and sodium nitrite. Since coffee (1 g/kg body weight) did not decrease DNA damage when administered orally together with performed methylnitrosourea, it was hypothesized that coffee inhibits nitrosation in the stomach of mice. The lowest effective level of coffee, when compared on the basis of body weight, corresponds to a human intake of about 5 cups of coffee. Both chlorogenic acid (150 mg/kg body weight) and premelanoidins (1 g/kg body weight), which occur as ingredients in, or are formed during roasting of, coffee, were shown to inhibit nitrosourea-induced DNA damage in mice.

Administration, Oral↗