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Molecular dosimetry of chemical mutagens: measurement of molecular dose and DNA repair germ cells

Description: Molecular dosimetry in the germ cells of male mice is reviewed with regard to in vivo alkylation of sperm heads, in vivo alkylation of sperm DNA, and possible alkylation of sperm protamine. DNA repair in male germ cells is reviewed with regard to basic design of experiments, DNA repair in various stages of spermatogenesis, effect of protamine on DNA repair following treatment with EMS or x radiation, and induction of DNA repair by methyl methanesulfonate, propyl methanesulfonate, and isopropyl methanesulfonate. (HLW)
Date: January 1, 1975
Creator: Sega, G.A.
Partner: UNT Libraries Government Documents Department

DNA repair in spermatocytes and spermatids of the mouse

Description: When male mice are exposed to chemical agents that reach the germ cells several outcomes are possible in terms of the germ cell unscheduled DNA synthesis (UDS) response and removal of DNA adducts. It is possible that: the chemical binds to the DNA and induces a UDS response with concomittant removal of DNA adducts; the chemical binds to the DNA but no UDS response is induced; or the chemical does not bind to DNA and no UDS is induced. Many mutagens have been shown to induce a UDS response in postgonial germ cell stages of the male mouse up through midspermatids, but the relationship between this UDS and the repair of genetic damage within the germ cells is still unknown. While some mutagens appear to have an effect only in germ-cell stages where no UDS occurs, others are able to induce genetic damage in stages where UDS has been induced.
Date: January 1, 1982
Creator: Sega, G.A.
Partner: UNT Libraries Government Documents Department

(Biological dosimetry)

Description: The traveler participated in an International Symposium on Trends in Biological Dosimetry and presented an invited paper entitled, Adducts in sperm protamine and DNA vs mutation frequency.'' The purpose of the Symposium was to examine the applicability of new methods to study quantitatively the effects of xenobiotic agents (radiation and chemicals) on molecular, cellular and organ systems, with special emphasis on human biological dosimetry. The general areas covered at the meeting included studies on parent compounds and metabolites; protein adducts; DNA adducts; gene mutations; cytogenetic end-points and reproductive methods.
Date: November 6, 1990
Creator: Sega, G.A.
Partner: UNT Libraries Government Documents Department

Adducts in sperm protamine and DNA (deoxyribonuclease) vs. mutation frequency

Description: In mammals, variability in the genetic sensitivity of different germ-cell stages to mutagens could be the result of how much chemical reaches the different stages, what molecular targets may be affected in the different stages and whether or not repair of lesions occurs. In the mouse, several mutagens have been found that cause their greatest genetic damage in late-spermatid and early-spermatozoa stages and that also bind very strongly to the protamine in these stages. Chemicals which are less genetically damaging to these stages have been found to have much less affinity for protamine. Furthermore, the level of chemical binding to DNA in late-spermatid and early-spermatozoa stages has not been correlated with the level of induced genetic damage, although DNA breakage in these sensitive stages has been shown to increase. This DNA damage is believed to indirectly result from chemical binding to sulfhydryl groups in protamine which prevents normal chromatin condensation within the sperm nucleus. 16 refs., 5 figs.
Date: January 1, 1990
Creator: Sega, G.A.
Partner: UNT Libraries Government Documents Department

Relationship between unscheduled DNA synthesis and mutation induction in male mice

Description: Unscheduled DNA synthesis (UDS) induced in the germ cells of male mice by chemical and physical agents can be studied in vivo by making use of the timing of spermatogenesis and spermiogenesis. In meiotic and post-meiotic germ-cell stages UDS occurs from leptotene through mid-spermatid stages but is not detected in later stages. No consistent correlation has been seen between the occurrence of UDS in the germ cells and reduced dominant-lethal frequencies or reduced specific-locus mutation frequencies. It is suggested that the UDS observed in the germ cells may be principally involved in the removal of DNA lesions which, if left, could give rise to subtle genetic damage that current mammalian genetic tests may not be able to detect. Characterization of mouse stocks with reduced UDS capability in their germ cells plus the development of biochemical genetic markers that can measure single amino acid substitutions will likely be necessary before the relationship between UDS in mammalian germ cells and repair of genetic damage can be clearly established.
Date: January 1, 1979
Creator: Sega, G. A.
Partner: UNT Libraries Government Documents Department

Radiation dosimetry in experimental animals exposed to tritiated water under different conditions. [Comparison between single injection and protracted low-level exposures in mice]

Description: The radiation dose to the germ cells of male mice, which sired the offspring scored in a specific-locus mutation test of injected tritiated water, was calculated. The weighted mean dose for germ cells which received all of the radiation at postspermatogonial stages was 430 rads, while that for germ cells irradiated almost entirely as spermatogonia was 615 rads. Most of the animals received a single intraperitoneal injection of HTO of 0.50 mCi/g body weight, but a few of them received 00.75 mCi/g. These weighted mean doses reflect the contribution of both groups. The percentage of the total dose delivered from /sup 3/H incorporated into macromolecules is small - less than 0.5%. The percentage of the total radioactivity in dry material from the testis on day 1 postinjection is 0.6%, on day 7 it is 3.2%, and on day 605 it is 95%. Tritium is incorporated into testicular DNA from tritiated water, and peak levels of radioactivity in this macromolecule are reached from 3 to 9 days following injection. The stable incorporation of tritium into trichloracetic acid insoluble materials is about 75% in protein and 25% in nucleic acids at all time periods following injection. Doses from single injections of tritiated water are inherently more variable than for protracted low-level exposures. This is because small differences in water balance near the time of injection can make a very large difference in total radiation dose.
Date: January 1, 1978
Creator: Cumming, R.B.; Sega, G.A. & Walton, M.F.
Partner: UNT Libraries Government Documents Department

Molecular targets, DNA breakage, DNA repair: Their roles in mutation induction in mammalian germ cells

Description: Variability in genetic sensitivity among different germ-cell stages in the mammal to various mutagens could be the result of how much chemical reaches the different stages, what molecular targets may be affected in the different stages and whether or not repair of lesions occurs. Several chemicals have been found to bind very strongly to protamine in late-spermatid and early-spermatozoa stages in the mouse. The chemicals also produce their greatest genetic damage in these same germ-cell stages. While chemical binding to DNA has not been correlated with the level of induced genetic damage, DNA breakage in the sensitive stages has been shown to increase. This DNA breakage is believed to indirectly result from chemical binding to sulfhydryl groups in protamine which prevents normal chromatin condensation within the sperm nucleus. 22 refs., 5 figs.
Date: January 1, 1989
Creator: Sega, G.A.
Partner: UNT Libraries Government Documents Department

The Hydrolysis of Di-Isopropyl Methylphosphonate in Ground Water

Description: Di-isopropyl methylphosphonate (DIMP) is a byproduct from the manufacture of the nerve agent Sarin. The persistence of DIMP in the ground water is an important question in evaluating the potential environmental impacts of DIMP contamination. The half-life of DIMP in ground water at 10 deg C was estimated to be 500 years with a 95% confidence interval of 447 to 559 years from measurements of the hydrolysis rates at temperatures between 70 to 98 deg C.Extrapolation of the kinetics to 10 deg C used the Arrhenius equation, and calculation of the half-life assumed first-order kinetics. Inorganic phosphate was not detected.
Date: December 31, 1997
Creator: Sega, G.A., Tomkins, B.A., Griest, W.H., Bayne, C.K.
Partner: UNT Libraries Government Documents Department

The Quantitation of Sulfur Mustard By-Products, Sulfur-Containing Herbicides, and Organophosphonates in Soil and Concrete

Description: Over the past fifty years, the facilities at Rocky Mountain Arsenal have been used for the manufacturing, bottling, and shipping sulfur- containing herbicides, sulfur mustard, and Sarin. There is a need for analytical methods capable of determining these constituents quickly to determine exactly how specific waste structural materials should be handled, treated, and landfilled.These species are extracted rapidly from heated samples of soil or crushed concrete using acetonitrile at elevated pressure, then analyzed using a gas chromatograph equipped with a flame photometric detector. Thiodiglycol, the major hydrolysis product of sulfur mustard, must be converted to a silylated derivative prior to quantitation. Detection limits, calculated using two statistically-unbiased protocols, ranged between 2-13 micrograms analyte/g soil or concrete.
Date: December 31, 1997
Creator: Tomkins, B. A.
Partner: UNT Libraries Government Documents Department