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Biomedical subjects

M S Legator

Publications and source records attributed to M S Legator.

At least 91 records · Page 5Linked to original sources
PubMed1983

Clastogenic effects of transplacental exposure of mouse embryos to nitrogen mustard or cyclophosphamide.

Embryos from day 12 pregnant Swiss mice given intraperitoneal injections of nitrogen mustard (HN2) or cyclophosphamide (CP) were evaluated for chromosomal aberrations. Both agents induced dose-dependent increases in the frequency of cells with aberrations observed in embryos from females treated 6 hr before sacrifice. The highest frequencies of cells with aberrations were observed when females were injected 15 or 18 hr before sacrifice on day 12. A teratogenic dose of HN2 (1.0 mg/kg) induced significantly higher frequencies of damaged cells than a teratogenic dose of CP (20 mg/kg). Cytogenetic analysis of rodent embryos from pregnant females exposed to xenobiotic agents may be an effective screening test for evaluation of genetic effects induced by transplacental exposure.

Animals↗
PubMed1983

The identification and characterization of a urinary mutagen resulting from cigarette smoke.

The urine of a cigarette smoker who excretes exceptionally mutagenic urine was analyzed for several factors affecting mutagenicity. S. typhimurium strain TA98 was always more sensitive to XAD-2 urine concentrates than TA100. With TA98, as high as 85 revertants per ml of urine were produced. It was observed that incubation with beta-glucuronidase was not required for expression of mutagenicity but that a complete S9 mix was needed to convert the material in the concentrate to the ultimate mutagenic species. TLC and HPLC separation of the XAD-2 urine concentrate resulted in the identification of trace amounts of the bladder carcinogen, 2-aminonaphthalene (beta-naphthylamine) and a considerable amount of a possible metabolite of 2-aminonaphthalene, 2-amino-7-naphthol. The identity of the compounds was confirmed by mass spectral analysis, and 2-amino-7-naphthol was shown to be a mutagen for TA100 and TA98 when activated by rat-liver S9.

Animals↗
PubMed1983

The evaluation of mutagenicities of 19 structurally related aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100.

19 aromatic amines were assayed for mutagenicity using Salmonella typhimurium strains TA98 and TA100 with and without the addition of S9 from Aroclor-1254-induced rat liver. These included: naphthalenes (1-amino-, 1-acetamido-, 2-amino-, 2-acetamido-, 1-amino-4-nitro- and 2-amino-1-nitro-), biphenyls (2-amino-, 2-acetamido-, 4-amino- and 4-acetamido-), fluorenes (2-amino- and 2-acetamido-), anthracenes (1-amino-, 1-acetamido-, 2-amino- and 2-acetamido-), 3-aminofluoranthene, 1-aminopyrene and 6-aminochrysene. None of the compounds were mutagenic when tested without S9. With S9, 15 of 19 were mutagenic for TA98 and 16 of the 19 were mutagenic for TA100. Overall, 2-aminoanthracene was the most potent mutagen. When compared to the parent amines, the respective acetamido derivatives were consistently less mutagenic.

Acetamides↗
PubMed1983

Dominant lethal effects of n-butyl glycidyl ether in mice.

Using the dominant lethal assay, the ability of n-butyl glycidyl ether to induce mutations in male mice was investigated. No significant dose-related changes either in pregnancy rates or in average number of implants per pregnant female were found. However, while the results were not altogether conclusive, there was evidence of a significant increase in fetal death rates by the end of the first week after the highest dosage was administered.

Animals↗
PubMed1983

Post-meiotic cell mediation of behavior in progeny of male rats treated with cyclophosphamide.

Transmission of the effects of paternal pre-fertilization exposure to a genotoxic drug being manifested in the F1 progeny is well established using the traditional rodent dominant lethal protocol [7]. More recently, the induction of genotoxic effects in the F1 progeny following chronic paternal exposure prior to fertilization has been described in rats using behavioral testing as an endpoint [1]. In our initial study, male F344 adult rats were treated chronically with 10 mg/kg cyclophosphamide (CP) or saline for 5 weeks (5 days of daily treatment and 2 days of rest). The present study describes the behavior of progeny whose fathers were treated with a single intraperitoneal injection of 10 mg/kg CP and mated at different times post-injection. This design showed that post-meiotic germ cells are the most sensitive to the effects of CP as seen by behavioral testing of the F1 progeny.

Animals↗
PubMed1982

An evaluation of the host-mediated assay and body fluid analysis. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The methodologies and status of the Host-Mediated Assay were reviewed using the published literature available up to June 1980. The Working Group reviewed 274 documents, including abstracts, research articles, review articles, and publicly available contracts and grant final reports. From this group, abstracts and reviews were rejected from critical evaluation. 77 documents were accepted and reviewed by the Working Group and the test results summarized. These selected documents yielded 208 chemicals that were evaluated in th host-mediated assay. Of these chemicals, 133 were mutagenic in this assay with one or more indicators. 76 chemicals, several of which are not considered to be carcinogenic, were not detected by any of the indicators. Of the 208 chemicals, 125 had been tested in carcinogenicity assay in rodents. 90, or 71%, of the carcinogens were detected as mutagens in the Host-Mediated Assay. In several cases, those carcinogens not detected may have been negative because of improper selection of the indicator. The Working Group concluded that the Host-Mediated Assay is an important test in mutagenicity/carcinogenicity research and that, by proper selection of protocols and indicators, valuable information can be gained that otherwise would be overlooked strict, in vitro assays.

Animals↗
PubMed1982

Unscheduled DNA synthesis induced in human lymphocytes by butyl glycidyl ethers.

Unscheduled DNA synthesis (UDS) was examined in normal human peripheral blood lymphocytes (HPBL) exposed to n- and tert.-butyl glycidyl ethers (BGE). n-BGE, which is currently used as a major reactive diluent for industrial epoxy resin systems, has been implicated as a bacterial mutagen. t-BGE, a potential replacement for n-BGE, is less cytotoxic to HPBL. Both these BGEs have demonstrated genetic activity in human cells. Here, slide autoradiography and liquid scintillation counting techniques have been used to show that both n-BGE and t-BGE induce repair-DNA synthesis in normal HPBL. These agents demonstrate similar dose-response relationships over the range of concentrations up to 333 micrograms/ml. Cultures were examined for repair-DNA synthesis after a continuous 5-h exposure to varying concentration of n-BGE or t-BGE.

Cell Survival↗
PubMed1981

Cyclophosphamide-induced spermatogenic effects detected in the F1 generation by behavioral testing.

Fischer 344 male rats were treated with cyclophosphamide (10 milligrams per kilogram of body weight) for 5 weeks and subsequently mated to females previously treated with saline or cyclophosphamide. The F1 progeny of the cyclophosphamide-treated males exhibited behavior deficits when compared to controls. These data could indicate a chemically induced genetic effect manifested by behavioral alterations.

Animals↗
PubMed1981

Herpes virus inactivation by chemical carcinogens: differential inactivation of herpes simplex viruses by 4-nitroquinoline 1-oxide and related compounds.

Treatment of stocks of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) with the chemical carcinogen 4-nitroquinoline 1-oxide (NQO) resulted in inactivation of virus infectivity at rates which were directly dependent on the concentration of NQO and interval of exposure to NQO. HSV-1 strains were more sensitive than HSV-2 strains to inactivation by NQO, although survival curves of both HSV types were multicomponent. Exposure of HSV-2 to a related group of chemicals suggested that the structural specificity required for inactivation of this virus was similar to that established by previous in vivo carcinogenicity tests.

4-Nitroquinoline-1-oxide↗
PubMed1981

Etiology, role and detection of chromosomal aberrations in man.

Genetic aberrations play a major role in human disease. They are responsible for a number of birth defects and have been identified as an important cause of much prenatal mortality. Approximately one-half of all conceptuses, for example, have been estimated not to survive to term, and some die so early that they are not even detected by the mother. Not all genetic anomalies appear at birth, however, since a number may result postnatally from environmental agents that have caused single cell mutations (which might develop into a human tumor), and yet others may require a second mutational event and appear even later. Thus, the industrial environment poses special hazards, to both female and male workers, because of the risks of induction of cancer, as well as of impairment of reproductive ability. Industrial cytogenetic monitoring, as a form of preventive medicine, is now possible. This review discusses many of the causes and types of genetic damage and the current cytogenetic techniques, as well as their use in industrial monitoring.

Animals↗
PubMed1981

Mutagenicity studies of vinyl chloride.

Mutagenicity studies in both man and in test organisms clearly demonstrate positive mutagenic activity of vinyl chloride. In terms of the mutagenicity studies using a variety of in vitro procedures covering both eukaryotes and prokaryotes, positive effects were found. Cytogenetic in vivo studies in animals and in humans indicate not only somatic mutations, but also germinal effects with this chemical.

Animals↗
PubMed1980

Sex-related differences in cytogenetic effects of benzene in the bone marrow of Swiss mice.

Two routes of administration-intraperitoneal injection and oral gavage-and two methods of analysis-direct metaphase preparations and the micronucleus test-were used to investigate the cytogenetic effects of benzene exposure in the bone marrow of female and male Swiss (CD-1) mice. The males demonstrated higher mean frequencies of metaphase aberrations and micronuclei after both routes of administration. The frequencies of metaphase aberrations appeared to be sex-related and independent of the route of exposure, however, while the frequencies of micronuclei appeared to be dependent upon both the sex of the animals and the route of administration.

Animals↗
PubMed1980

The evaluation of the epoxide diluent, n-butylglycidyl ether, in a series of mutagenicity assays.

The epoxide diluent, n-butylglycidyl ether (n-BGE), was tested in vitro for mutagenicity using Salmonella typhimurium and for transforming ability in mouse embryo cells (BAlb/3T3-A31-1-13). The n-BGE produced base-pair type mutations in S typhimurium strains TA1535 and TA100. However, it failed to transform mouse embryo cells when assayed up to toxic levels. The mutagenic activity could not be detected in the urine of mice, although several doses, routes of administrations, and lengths of exposure were examined. Orally administered n-BGE did not produce any increase in micronuclei in mice, but when the diluent was administered intraperitoneally, either one or two times, dose-related increases in the number of micronuclei were observed.

Animals↗
PubMed1980

Correlation of the chemical structure of 4-nitroquinolines inactivating human cytomegalovirus and established in vivo carcinogenicity tests.

Inactivation of the infectivity of human cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) has been observed following exposure to 4-nitroquinoline 1-oxide (NQO) or its metabolite, 4-hydroxyaminoquinoline 1-oxide (HAQO). The present study of the specificity of the chemical structure of 4-nitroquinolines demonstrated that both the 4-nitro and 1-oxide groups were required for inactivation of virus infectivity. Reduction of the 4-nitro group to a 4-hydroxyamino group enhanced activity, while further reduction to an amino group resulted in loss of activity against virus infectivity. The capacity to inactivate virus was also lost by substitution of the pyridine ring for the quinoline nucleus of NQO. The relationship between the chemical structure and the ability to inactivate viruses studied here correlates well with earlier in vivo carcinogenicity studies of the same group of chemicals.

4-Nitroquinoline-1-oxide↗
PubMed1980

The mutagenic evaluation of tetrakis (hydroxymethyl) phosphonium sulfate using a combined testing protocol approach.

This study was undertaken to evaluate the mutagenicity of the flame retardant, Tetrakis (Hydroxymethyl) Phosphonium Sulfate -75% or its possible metabolic products using a battery of in vitro and in vivo assays. The starting material in the fabric treatment process, THPS was tested with five strains of Salmonella typhimurium with and without the addition of a rat liver activating system. In addition, the THPS and the treated fabric were assayed in a combined testing protocol. The mutagenicity tests which were employed in this protocol included (a) the analysis of the urine of treated mice, (b) the micronucleus test, and (c) metaphase analysis. The animals were administered the THPS both orally and dermally and the treated fabric was incorporated into the animals' feed. The THPS produced no mutagenic response in any of the strains of S. typhimurium either when tested directly or with the addition of Acroclor--or phenobarbital-- induced rat liver. The results of the combined testing protocol, with the three routes of administration, were also negative for the urine analysis, micronucleus test and metaphase analysis.

Administration, Oral↗