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Biomedical subjects

D J Brusick

Publications and source records attributed to D J Brusick.

At least 37 records · Page 2Linked to original sources
PubMed1986

The Salmonella typhimurium/mammalian microsomal assay. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The Salmonella assay has been in use for almost 15 years and can be defined as a routine test for mutagenicity and for predicting potential carcinogenicity. It detects the majority of animal carcinogens and consequently plays an important role in safety assessment. The test is also routinely used as the frontline screen for environmental samples (complex mixtures) isolated from air, water and food. This role will continue to remain an area of growth as or because sample volumes associated with these testing areas are generally very limited and more extensive testing is generally impossible. While this test, like all others, has some limitations, it is recommended that it be regularly included in all genetic testing batteries.

Animals↗
PubMed1986

Mutagenicity studies on FD&C red No.3.

FD&C Red No.3 (erythrosine) has been used as a dye in foods, drugs and cosmetics since its approval by the US Department of Agriculture in 1907. In 1977 the Certified Color Manufacturers' Association (CCMA) initiated studies on FD&C Red No.3 including chronic toxicity and carcinogenicity studies in rats and mice. Data from the CCMA chronic studies revealed an increased incidence of thyroid follicular cell hyperplasia and adenomas in male rats that received 4% FD&C Red No.3 in the diet (2464 mg/kg/day) during life-time (30 months) following in utero exposure. In this report, results of published studies on the mutagenicity of FD&C Red No.3 are critically reviewed. Additional mutagenicity tests including Ames Salmonella/microsome assay, L5178Y TK+/- mouse lymphoma assay, mouse micronucleus test and mitotic recombination assay with yeast Saccharomyces cerevisiae strain D5 are described. These test results together with the literature review indicate that FD&C Red No.3 can be considered non-mutagenic across several genetic endpoints including gene mutation, chromosome aberrations, primary DNA damage and cell transformation. The results of the genotoxicity assessment generally exclude FD&C Red No.3 as a genotoxic initiator and suggest that some other mechanism is responsible for the increase in tumors.

Animals↗
PubMed1986

Genotoxicity of hexachlorobenzene and other chlorinated benzenes.

Hexachlorobenzene (HCB) and other chlorinated benzenes have had only limited mutagenicity evaluation but tests have shown a general lack of evidence for mutagenicity. Bacterial reverse mutation studies have been typically negative and only a few studies on cultured mammalian cells have been published. Recent reports indicate that HCB does not induce sister chromatid exchange or DNA-strand breakage in vitro. A single report of HCB-induced reverse mutation in yeast is suspect due to the failure to establish either dose-response effects or an acceptable level of statistical significance. In-vivo data are limited primarily to dominant lethal studies in rats and some in-vivo alkaline elution results. Both types of tests revealed no genetic activity for HCB. A number of chlorine-substituted nitrobenzenes are positive in the Ames Salmonella reverse mutation assay, but when tested in eukaryotic cell assays, the results are generally negative. Ortho-, meta- and para-dichlorobenzenes are apparently mutagenic in Aspergillus nidulans, and para-dichlorobenzene has been reported to induce mitotic abnormalities in plant cells. Unscheduled DNA synthesis studies carried out with dichlorobenzenes proved negative. Monochlorobenzene failed to actively induce sister chromatid exchange in a human cell line. The only human data that have been reported for chlorinated benzenes involved accidental exposure of 26 people to ortho-dichlorobenzene vapours. Analysis of lymphocytes from this cohort suggested an increase in chromosome breakage.

Animals↗
PubMed1985

Basic principles of laboratory safety.

Laboratory safety is a concern to scientific personnel conducting research or safety testing, laboratory directors responsible for institutional liability for employees, and to individuals working or residing near the laboratory. A strategy for safe laboratory operations requires an understanding of industrial hygiene, engineering, and the regulations associated with the use of hazardous chemicals. This review describes many of the basic principles involved in laboratory safety. It provides general information on the use of personal protective equipment, selection of laboratory safety equipment, laboratory design, disposal of hazardous waste, and the regulations and guidelines affecting laboratory operations.

Accident Prevention↗
PubMed1984

Evaluation of the mutagenic potential of corn (Zea mays L.) grown in untreated and atrazine (AAtrex) treated soil in the field.

Bacterial assays using extracts from field corn plants (harvested at one month, silage and mature stages) do not indicate that soil treatment with atrazine, at its maximum use rate, alters the endogenous mutagens present in these extracts, nor that atrazine itself is degraded to mutagenic products. Extracts of corn grown in soil treated with AAtrex were equally mutagenic with those of corn grown in untreated soil when tested in Salmonella typhimurium TA-100 by a reversion assay or in Salmonella typhimurium TM-677 in a forward mutation assay. Higher concentrations of histidine in corn grown in AAtrex treated soil may interfere with the reversion assay, but do not affect the forward mutation assay. The nature of the agent(s) responsible for the positive response was not determined. The mutagenicity may be due to natural plant constituents, an artifact of the sample preparation, or mycotoxins from some unrecognized plant infection. The experimental results in these field studies do not show that atrazine is degraded or metabolized by corn plants to mutagens in this sensitive bacterial assay.

Atrazine↗
PubMed1983

Mutagenic evaluations of four rubber accelerators in a battery of in vitro mutagenic assays.

The mutagenic/carcinogenic potential of four commercial accelerators were evaluated using a battery of in vitro assays. All of these compounds were mutagenic in one or more assays. Positive responses were noted in the Escherichia coli pol A+/pol A- DNA repair, mouse lymphoma L5178Y TK+/- forward mutation, BALB/3T3 cell transformation, and CHO cell chromosome aberration assays. In contrast to previous studies of accelerators, no mutagenic response was observed in the E coli WP2 uvrA- assay or in any of the Salmonella typhimurium strains tested. These studies have indicated that rubber accelerators should be regarded as potential human health hazards and that further in vitro and in vivo studies are needed to assess the potential genetic hazards of this large class of chemicals.

Benzothiazoles↗
PubMed1983

Genotoxic properties of 2,4,7-trinitro-9-fluorenone.

The genotoxic effects of 2,4,7-trinitro-9-fluorenone (TNF) were studied in assays employing procaryotic (Salmonella typhimurium and Escherichia coli) and eucaryotic (Saccharomyces cerevisiae, mouse lymphoma L5178Y and Chinese hamster ovary) cells. The results show that TNF is a potent mutagen for procaryotes. It causes both frame-shift and base-pair substitution mutations, although frame-shift mutations were predominant. In Saccharomyces cerevisiae, this compound appeared to be too toxic to permit detection of genotoxic effects. TNF was also toxic to mouse lymphoma cells and Chinese hamster ovary cells but the toxic effects were reduced by metabolic activation. TNF induced a clear increase in sister-chromatid exchanges in CHO cells and in mutant frequency in mouse lymphoma cells both in the presence and absence of metabolic activation.

Animals↗
PubMed1982

The activity of 2-(2',4'-diaminophenoxy)ethanol in 3 genetic toxicity bioassays.

2-(2',4'-Diaminophenoxy)-ethanol, a hair-dye ingredient was evaluated for genetic activity in vitro using urine collected from mice in an Ames test and in vivo using the mouse dominant-lethal assay and the mouse spot test for somatic mutation detection. All 3 studies were conducted using dermal application of the dye material to shaved skin. The applied dose levels ranged from 15 to 1500 mg/kg body weight. The results of these 3 studies were considered to be negative although urine analysis and spot-test data showed non-significant dose-related increases.

Alleles↗
PubMed1981

Evaluation of the genetic activity of industrially produced carbon black.

Commercially produced oil furnace carbon black (Chemical Abstract Service Registry No. 1333-86-4) has been evaluated by five different assay for genetic activity. These were the Ames Salmonella typhimurium reverse mutation test, sister chromatid exchange test in CHO cells, mouse lymphoma test, cell transformation assay in C3H/10T1/2 cells, and assay for genetic effects in Drosophila melanogaster. Limited cellular toxicity was exhibited but no significant genetic activity was noted.

Air Pollutants↗
PubMed1980

An evaluation of the Escherichia coli WP2 and WP2 uvrA reverse mutation assay.

The methodology and status of the Escherichia coli WP2 reverse mutation system as it applies to chemical screening were reviewed using the available published literature. 163 documents were reviewed by the Working Group. These included abstracts, research articles, review articles and publicly available contract and grant final reports. From this group, 115 documents were rejected for critical evaluation by the Working Group. 48 documents were reviewed and the test results summarized. The general conclusion of the Working Group was the the E. coli WP2 reverse mutation system is a valuable tool for mutagenesis research, but that there is no evidence from a review of the literature that this assay will contribute significantly to the results obtainable from careful application of the Ames Salmonella assay. Another review of the role of this system in general screening may be warranted after more research and development with the plasmid-containing WP2 derivatives.

DNA Repair↗
PubMed1979

Lack of microbial genetic response to 2.45-GHz CW and 8.5- to 9.6-GHz pulsed microwaves.

Strain D4 of the yeast Saccharomyces cerevisiae, and strains TA-1535, TA-100 and TA-98 of the bacterium Salmonella typhimurium, were exposed to 2.45-GHz continuous wave or 8.5- to 9.6-GHz pulsed electromagnetic radiation (EMR) at various power densities from 1 to 45 mW/cm2. The temperature during radiation was maintained at 30 degrees C for yeast cultures and at 37 degrees C for bacterial cultures. The studies revealed no increase in mutations or of mitotic gene conversions when cells were radiated for two hours or less. Decreased viability of cells was noted in all cultures tested after radiation at power densities of 30 mW/cm2 or more; however, no reliable changes in genetic events occurred.

Electromagnetic Fields↗
PubMed1977

In vitro mutagenesis assays as predictors of chemical carcinogenesis in mammals.

In vitro microbial mutagenesis assays coupled with mammalian activation systems offer promising technique to screen chemicals for their potential carcinogenic activity. The correlation between mutagenic and carcinogenic properties for a large array of chemicals is approximately 0.9. The best correlation exists for those carcinogens which are themselves highly electrophilic or produce electrophilic metabolites. Correlation between mutagenicity and carcinogenicity for hormonal, metallic, or physical carcinogens has been disappointing but not unexpected based on their proposed mechanisms of action. In addition to the application of in vitro mutagenesis techniques to screening chemicals for the identification of potential carcinogens, they are useful tools for investigating genetic, biochemical, and pharmacologic properties of different animal species. Studies with the chemical carcinogen dimethylnitrosamine have been conducted and show a functional relationship between mutagenesis and carcinogenesis. The assays can also be conducted using activation systems prepared from the tissues of any mammalian species. This permits a direct assessment of phylogenic extrapolation by comparing the metabolic activation capabilities of tissues from several mammalian species, including human samples. The advantages of mutagenicity testing are the short period of time required for results, the high sensitivity of the assay (microgram of nanogram quantities of chemicals can be used), and the fact that the ultimate agent can be detected biologically without first necessitating chemical identification and isolation. It appears from current studies that in vitro mutagenesis techniques may well open new avenues of investigation into some old toxicologic problems.

Aging↗
PubMed1976

Genetic effects induced in Saccharomyces cerevisiae by cyclophosphamide in vitro without liver enzyme preparations.

Cyclophosphamide induced forward mutation in Saccharomyces cerevisiae strain S288C and mitotic recombination in strains D3 and D5 but not in strain D4. The yeast cells were treated with the compound in phosphate buffer without recourse to metabolic activation protocols. Elevation of the treatment temperature increased the genetic activity of cyclophosphamide. Respiration-deficient isolates of strains S288C and D3 were more sensitive than the respiratory competent parent strains were for inducing forward mutation and mitotic recombination, respectively. Cyclophosphamide was incubated in phosphate buffer alone for increasing time intervals; strain D3 cells were added to aliquots for each time interval and incubated for an additional 30 min. The frequency of induced recombination increased as the time of compound incubation increased, showing that spontaneous degradation of cyclophosphamide to genetically active breakdown products was responsible for the genetic damage induced in the yeast cells.

Cyclophosphamide↗