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D G Gosslee

Publications and source records attributed to D G Gosslee.

15 recordsLinked to original sources

Ethylene oxide dose and dose-rate effects in the mouse dominant-lethal test.

In the dose-response study, male mice were exposed by inhalation to ethylene oxide (EtO) for 4 consecutive days. Mice were exposed for 6 hr per day to 300 ppm, 400 ppm, or 500 ppm EtO for a daily total of 1,800, 2,400, or 3,000 ppm X hr (total exposures of 7,200, 9,600 and 12,000 ppm X hr), respectively. In the dose-rate study, mice were given a total exposure of 1,800 ppm X hr per day, also for 4 consecutive days, delivered either at 300 ppm in 6 hr, 600 ppm in 3 hr, or 1,200 ppm in 1.5 hr. Quantitation of dominant-lethal responses was made on matings involving sperm exposed as late spermatids and early spermatozoa, the most sensitive stages to EtO. In the dose-response study, a dose-related increase in dominant-lethal mutations was observed, the dose-response curve proved to be nonlinear. In the dose-rate study, increasing the exposure concentrations resulted in increased dominant-lethal responses.

Air Pollutants↗

Do spermatogonial stem cells have a circadian rhythm?

Mitotic index was determined in whole mounts of segments of seminiferous tubules of (101 X C3Hf)F1 male mice at 3 hr intervals from 18.00 to 06.00 hours, and at hourly intervals from 08.00 to 16.00 hours. The highest frequency of metaphase-anaphase figures occurred at 10.00 and 11.00 hours, but was not significantly higher than for other times. Injection of 25 mu Ci 3H-TdR per mouse, followed 24 hr later by exposure to 300 rad X-rays and killing 207 hr after labelling was used to test for circadian rhythm in DNA synthetic activity of the long-cycling As spermatogonia. No significant effect of time of day was observed. Likewise, the number of undifferentiated spermatogonia scored 183 hr after 300 rad showed no effect of time of day. The testis therefore appears to have no circadian rhythm in mitotic activity. Stage of the cycle of the seminiferous epithelium, however, showed a significant effect on mitotic index of As spermatogonia and on DNA synthetic activity of undifferentiated spermatogonia. These data are compared with those for other organisms and tissues in respect to which properties of stem cells are general for all organisms and tissues and which are specific for spermatogonia.

Animals↗

Patterns of cell proliferation during recovery from oxygen injury. Species differences.

Do rats, mice, hamsters, and marmosets respond differently to acute lung injury? Animals of each species were exposed to 100% oxygen for 48 h, then osmotic pumps, which released 3H-thymidine for a 1-wk period, were implanted. The labeling index (LI) (cells labeled/total cells counted) was increased in all 4 species. Repair in rats was manifested by a high LI, dominated by endothelial cell proliferation. Mice and hamsters had a lower LI, which was dominated by type II pneumocyte proliferation in mice, whereas in hamsters, macrophages and pneumocytes proliferated. The pattern of cell proliferation in marmosets most resembled that seen in mice.

Animals↗

Heritable translocation test in mice.

The status of the heritable-translocation test in mice with respect to its usefulness in practical testing was evaluated by using information available in the open literature. A total of 47 reports were evaluated; 29 were judged to contain adequate information to classify whether or not a given chemical induced heritable translocations. Heritable-translocation data were available for 32 compounds; data were not adequate for 15 compounds. Of the remaining 17 compounds, clear-cut determination of positive or negative effects was made for 14 compounds, while data for 3 compounds were only suggestive of either negative or positive effects. 10 chemicals have been shown to induce heritable translocations. These chemicals are either direct or indirect alkylating agents. The heritable-translocation test needs to be improved before it can be used in wide-scale practical testing. The most important question is whether or not historical controls can be used in tests for significance; the cost of concurrent controls is prohibitive. There is a need to standardize methods used in testing laboratories with respect to the size of error involved in classifying translocation heterozygotes and the power of the test. There is also a need to study in the effectiveness of non-alkylating clastogens in inducing heritable translocations in mice.

Animals↗

The dose-response relationship for ethyl methanesulfonate-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells.

The frequency of ethyl methanesulfonate (EMS)-induced mutations to 6-thioguanine resistance in a Chinese hamster ovary cells clone K1-BH4 was studied at many EMS doses including the minimally lethal range (0-100 microng/ml) as well as the exponential killing portion (100-800 microng/ml) of the survival curve. The mutation frequency increases approximately in proportion with increasing EMS concentration at a fixed treatment time. The pooled data for the observed mutation frequency, f(X), as a function of EMS dose X, is adequately described by a linear function f(X)=10(-6)(8.73+3.45 X), where 0 less than or equal to X less than or equal to 800 microng/ml. One interpretation of the linear dose-response is that, as a result of EMS treatment, ethylation of cellular constituents occurs, which is directly responsible for the mutation. Biochemical analyses demonstrate that most of the randomly isolated 6-thioguanine-resistant variants possess a highly reduced or undetectable level of HGPRT activity suggesting that the EMS-induced mutations to 6-thioguanine resistance affect primarily, if not exclusively, the HGPRT locus.

Animals↗

The dose-response relationship for ultraviolet-light-induced mutations at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster ovary cells.

Exposure of Chinese hamster ovary (CHO) cells clone K1BH4 to ultraviolet (UV) light at doses up to 86 ergs/mm2 did not significantly reduce cell survival, but UV doses of 86-648 ergs/mm2 produced an exponential cell killing. Observed mutation frequency ro 6-thioguannine resistance induced by UV increases approximately in proportion to increasing doses up to 260 ergs/mm2 in a range of 5-648 ergs/mm2 examined. The pooled data of mutation frequency f(X) as a function of dose X from 0-260 ergs/mm2 is adequately described by f(X)=10(-6) (13.6 + 2.04 X). That the UV-induced mutations to 6-thioguanine resistance affects the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus is supported by the observation that all randomly isolated drug-resistant colonies contained highly reduced or undetectable HGPRT activity.

Animals↗

Effects of dose on the induction of dominant-lethal mutations and heritable translocations with ethyl methanesulfonate in male mice.

Genetic damage by ethyl methanesulfonate (EMS) in male mice was measured at doses ranging from 50 to 300 mg/kg with dominant-lethal mutations and reciprocal translocations as endpoints. No appreciable increase in dominant-lethal mutations was detected following a dose of 100 mg/kg. Dominant lethals induced by EMS were convincingly detected only after a dose of 150 mg/kg, but in the translocation experiment an increase in the genetic effect was detectable at the 50 mg/kg dose. It is likely that dominant lethals had also been induced at the 50 and 100 mg/kg doses, but were not detected due to the relative insensitivity of the dominant..lethal procedure. Thus, for detection of low levels of EMS-induced chromosome breakage, translocations are a much more reliable endpoint than are dominant-lethal mutations. A procedure for large-scale screening of induced translocations is described.-The dominant-lethal dose-response curve, plotted on the basis of living embryos as a percentage of the control value, is clearly not linear as it is markedly concave downward. Similarly, the translocation dose-response curve showed a more rapid increase in the number of translocations with dose than would be expected on the basis of dose-square kinetics. It is clear for both of these endpoints that the effectiveness of EMS in inducing chromosome breakage is proportionately much lower at low doses.

Animals↗

Difference in the response of two hybrid stocks of mice to X-ray induction of chromosome aberrations in spermatogonial stem cells.

Ionizing radiation induces balanced reciprocal translocations in spermatogonial stem cells of mice. From cells carrying these rearrangements, which can be scored cytologically in the diakinesis-metaphase I stage, balanced normal, balanced translocated and unbalanced (duplication/deficiency) sperm can be produced. The relationship between expected (calculated from cytological data) and observed frequencies of embryonic lethality (presumably as a result of unbalanced sperm fertilizing the egg) following exposure of spermatogonial stem cells to X-rays was studied in two hybrid stocks. A marked difference in the incidence of induced embryonic lethality was found between the two stocks. Similarly, a difference in the cytological frequencies of translocations was also found, although smaller than that observed for embryonic lethality. Thus, it appears that the difference between the two stocks in the frequencies of embryonic lethality may be attributable both to processes occurring prior to metaphase I and to a difference in the rate of transmission of unbalanced chromosome constitutions.

Animals↗

Quantitative aspects of metal ion content and toxicity in Drosophila.

As a basis for both a genetic and a biochemical approach to a study of metal ion effects, a method for quantitating the toxic response of Drosophila to metal ions was developed. The response to 13 metal ions has been examined, including several chemical groups from the periodic table: the IIb ions Zn2+, Cd2+, and Hg2+; the IIa ions, Be2+, Mg2+, Sr2+, and Ba2+; the transition elements, Ni2+, Cu2+, Co2+, and Mn2+: and trivalent ions, Y3+ and Cr3+. The standard test procedure provides estimates of the median lethal concentration (LC50) and the range of the tolerance distribution both of which are obtained by the method of probit transformation. Range is defined as the change in concentration between the LC2.5 and the LC97.5. Estimation of range as the measure of the limits of the tolerance distribution was utilized to measure variation in the response to metals with time. Genetic characterization of strains will require strains of flies without overlapping tolerance ranges. Although there was a general trend of increasing values of range with increasing LC50 values, the exceptions (e.g., Cr3+ and Be2+) indicated that several factors may be involved in determining the range of lethal responses. Elemental analyses have been performed on flies before and after metal ion treatments to establish the amount of metal ion taken up and baselines for comparison. This study provides additional evidence that Drosophila is an appropriate organism for the study of specific biochemical alterations induced by metals, e.g., the cadmium-induced increase in Q(+)tRNAs.

Animals↗