Diagnostic quiz #43. Case no. 1. All of the above.
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Biomedical subjects
Publications and source records attributed to A Auletta.
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This paper reviews the ability of a number of chemicals to induce sister-chromatid exchanges (SCEs). The SCE data for animal cells in vivo and in vitro, and human cells in vitro are presented in 6 tables according to their relative effectiveness. A seventh table summarizes what is known about the effects of specific chemicals on SCEs for humans exposed in vivo. The data support the concept that SCEs provide a useful indication of exposure, although the mechanism and biological significance of SCE formation still remain to be elucidated.
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Since its development by Dr. Bruce Ames and his coworkers, the Salmonella typhimurium/mammalian microsome mutagenicity assay has been used widely throughout the world. Many authors have suggested various modifications and made recommendations in regards to this assay. Although the recommendations of a panel of experts was published in 1979 by de Serres and Shelby, a committee of members of the Environmental Mutagen Society (EMS) initiated this effort in response to the encouragement by the American Society of Testing and Materials (Committee E47.09.01) and because of new developments within the field of microbial mutagenesis testing. Its purpose is to provide a guide for people who perform or evaluate microbial mutagenesis tests, but it is not intended for these recommendations to replace or diminish the usefulness of presently available protocols and procedures.
The term dominant lethal may be defined as death of the heterozygote arising through multiple chromosomal breaks. The assay is generally conducted by treating male animals, usually mice or rats, acutely (1 dose), subacutely (5 doses), or over the entire period of spermatogenesis. Animals treated acutely or subacutely are mated at weekly intervals to females for a sufficient number of weeks to cover the period of spermatogenesis. Those treated for the entire spermatogenic cycle are mated for 1 or 2 successive weeks at the termination of treatment. Females usually are killed at 14 days of pregnancy and examined for the number of total implantations in the uterus, the number of implantations classified as early deaths, and, in some cases, the number of corpora lutea. The category of early death is the most significant index of dominant lethality. A total of 249 papers were reviewed and 140 chemicals were evaluated. Of the 140 chemicals, 65 were positive by the criteria used by the Work Group in evaluating each publication. The category of "positive" includes those responses of a borderline nature. 99 chemicals were declared negative. There is considerable overlap of chemicals in both categories, which accounts for the incongruity in the total number of chemicals tested and the number considered positive and negative. A total of 44 animal carcinogens have been tested in the dominant lethal assay, 26 of which were positive and 18 negative for a correlation of 59%. The role of the assay should be that of confirming positive results from lower tier chromosomal aberration-detecting systems (confirming in the sense of indicating the ability of the chemical to penetrate gonadal tissue and to produce cytogenetic damage). The dominant lethal assay should not be used as a risk assessment method.
Scientists in the Health and Environmental Review Division (HERD), Office of Toxic Substances of the U.S. Environmental Protection Agency, are examining the feasibility of expanding efforts in short-term carcinogen testing. Three areas for consideration have been defined. These are (1) short-term in vitro tests; (2) short-term in vivo tests; and (3) tumor markers. HERD's current efforts in short-term in vitro testing are exemplified by the Gene-Tox program. Through a comprehensive system of committees and reviews, the published literature on eukaryotic and prokaryotic in vitro and in vivo test systems are being examined and analyzed. The suitability of utilizing the various systems in a test battery to identify potential chemical mutagens and carcinogens will be ascertained. A review of the literature on short-term in vivo tests (limited bioassays) and tumor markers is currently being conducted. Correlations will be made between results obtained from these tests and epidemiological information and long-term animal bioassays. The attributes and deficiencies of each test or marker will be examined. Further testing, development, or validation needs will be outlined. The aim of this review is to attempt to expand the prechronic test battery for carcinogenicity in order to provide sufficient information for regulatory decision-making.
The GENE-TOX program, a two-phase evaluation from the existing literature of selected bioassays for detecting mutagenicity and presumptive carcinogenicity, is described. Sponsored and directed by the Office of Testing and Evaluation within the U.S. Environmental Protection Agency's (EPA) Office of Pesticides and Toxic Substances, this program will aid EPA in establishing standard genetic testing and evaluation procedures for the regulation of toxic substances and determining the direction of research and development in the area of genetic toxicology.
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Rubella virus specific hemagglutinating antigen was prepared in the fluid phase of suspension cultures. Systems employing baby hamster kidney culture adapted inocula, nonadapted inocula, and cells derived from long-term infected suspension cultures were evaluated. Optimal specific hemagglutinating titers were obtained when kaolin-treated fetal bovine serum was used in the media and when the incoulum had previously been adapted in a suspension culture system. When cultures derived from long-term infected suspension systems were studied, the number of daily harvests in which acceptable titers were present was prolonged. However, titers were generally higher in suspension systems employing cells which had recently been infected.
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