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Biomedical subjects

W M Generoso

Publications and source records attributed to W M Generoso.

At least 55 records · Page 3Linked to original sources
PubMed1986

Difference between two hybrid stocks of mice in the incidence of congenital abnormalities following X-ray exposure of stem-cell spermatogonia.

Unbalanced (duplication/deficiency) sperm from balanced reciprocal translocations induced in spermatogonial stem cells of mice generally lead to embryonic lethality around the time of implantation. In a recent study (Generoso et al., 1985), it was found that the incidence of X-ray-induced embryonic lethality differed markedly between two hybrid stocks of irradiated male mice. A parallel difference in the frequencies of reciprocal translocations was observed cytologically in the meiocytes of irradiated males. In the present report, which is an adjunct to the study by Generoso et al. (1985), it was determined whether or not similar differences between the two stocks exist for congenital defects resulting from genetic damage to stem-cell spermatogonia. The results indicate not only an association between the frequencies of induced reciprocal translocations and congenital abnormalities, but also a parallel greater frequency of induced malformations in the (C3H X 101)F1 stock versus the (SEC X C57BL)F1 stock of males.

Abnormalities, Radiation-Induced↗
PubMed1985

239Plutonium-induced heritable translocations in male mice.

This study was conducted to estimate the frequency of transmitted reciprocal translocations per rad of exposure to alpha particles from [239Pu]citrate. Data indicate that the rate of induction of heritable translocations is related linearly to the duration of spermatogonia stem cell exposure. The estimated increase in heritable translocations per rad of exposure of the stem cell to alpha particles is in the range of 1.45-2.91 X 10(-5)/gamete.

Animals↗
PubMed1985

Ethanol-induced late fetal death in mice exposed around the time of fertilization.

In the mouse, all autosomal monosomies and trisomies are lethal by the time of birth (Searle, 1981). To test whether ethanol ingested by females shortly after mating induces nondisjunction, as reported by Kaufman (1983) on the basis of cytological evidence, we attempted to determine whether the incidence of intrauterine death was affected by this treatment. The incidence of late death (day 11 postconception or later) was found to be significantly increased when ethanol was administered 2 h following a 30-min mating period, but not when the interval was shorter. Measurements of early death were not sensitive enough (because of the high control frequency) to show an effect of ethanol treatment. Limited cytological data showed an induced incidence of trisomy in line with the excess frequency of late death, but the trisomy incidence by itself was not significantly different from control. The overall level of effect in the present experiment was lower than that reported by Kaufman.

Animals↗
PubMed1984

Analysis of spontaneous early embryonic lethality in mice.

The incidence of spontaneously occurring deciduomata is considerably higher in T-stock than in (C3H X C57BL)F1 females. The basis for this difference was studied in vivo, by means of embryo transplantation procedure, and in vitro, by means of short-term embryo culture. Both studies indicate that strain differences in the incidence of spontaneous deciduomata may be largely, if not wholly, accounted for by genetic differences between embryos themselves expressed in terms of the rate of development during the preimplantation period and in the ability to survive the preimplantation and early implantation environment.

Animals↗
PubMed1984

Response of mouse spermatogonial stem cells to X-ray induction of heritable reciprocal translocations.

Although heritable translocations are an important endpoint for the assessment of genetic risk from radiation, there has been a serious information gap with regard to their induction in spermatogonial stem cells, the most important cell stage in males for risk considerations. This led to uncertainty in estimating the magnitude of risk per unit exposure. Further, the relationship between the frequency of reciprocal exchanges scored by cytological analysis of the exposed male's meiocytes and the frequency of those transmitted to first-generation offspring needed to be re-examined. In order to fill in these gaps, two radiation studies, i.e., dose response and dose fractionation, were conducted on spermatogonial stem cells in which heritable and cytologically detected translocations were scored. The present data are by far the most extensive, to date, for heritable translocation induction in spermatogonial stem cells. The linearity of the rising portion of the dose-effect curve and the additivity of effects observed in the fractionation study allow a direct estimation of the number of transmissible translocations expected per unit exposure. Thus, the expected increase in heritable translocations per rad of acute X-rays is 3.89 X 10(-5) per gamete. The data also show a lack of consistency between cytologically and genetically scored translocations.

Animals↗
PubMed1984

Pseudo dominant-lethal response in female mice treated with plant oils.

Corn oil, sesame oil, peanut oil, or olive oil, injected intraperitoneally to female mice prior to insemination, increased the number of deciduomata. In many plant oil-treated females the number of implantation sites was markedly higher than corpora lutea count. These effects were not observed among females that were treated similarly with mineral oil or among females that were given corn oil via oral administration. Evidence indicates that these effects did not arise from induced dominant-lethal mutations but from decidual responses resulting from traces of oil reaching the uterine lumen.

Animals↗
PubMed1982

Lack of association between induction of dominant-lethal mutations and induction of heritable translocations with benzo[a]pyrene in postmeiotic germ cells of male mice.

Benzo[a]pyrene was tested for induction of dominant-lethal mutations in germ cells of male mice. Clear-cut dominant-lethal effects were induced in middle and early spermatozoa. In contrast to the dominant-lethal observed the study showed no detectable increase in heritable translocations for these stages over the spontaneous level. Thus, the results provide another example of a chemical mutagen that is effective in inducing dominant-lethal mutations but relatively ineffective in inducing heritable translocations in male postmeiotic germ cells.

Animals↗
PubMed1982

Difference in the ratio of dominant-lethal mutations to heritable translocations produced in mouse spermatids and fully mature sperm after treatment with triethylenemelamine (TEM).

The relative induction of dominant-lethal mutations and heritable translocations in triethylenemelamine-treated postmeiotic germ cells of mice was determined depending on the stage treated. Males were mated either 11.5-14.5 days after treatment (middle spermatids) or less than 2.5 hours after treatment (fully mature sperm). Results clearly showed that, even through similar levels of dominant-lethal mutations were induced in fully mature sperm and in middle spermatids, the frequency of heritable translocations induced in mature sperm was markedly lower than that induced in middle spermatids. This observation was used, together with earlier ones, to suggest a mechanism by which dominant-lethal mutations and heritable translocations are produced following chemical treatment of male postmeiotic germ cels.

Animals↗
PubMed1981

Comparison of two methods for detecting translocation heterozygotes in mice.

An accurate estimate of the error of misclassifying male translocation heterozygotes as normals is essential for the proper evaluation of results of the heritable translocation test in mice. The size of this error may vary from one laboratory to another depending, primarily, on the method or variation of the method used in screening for translocation heterozygotes. This report shows a way to estimate for misclassification errors involved in two methods, sequential and direct cytological analysis, of screening for translocation heterozygotes. A positive correlation was found between the degree of partial sterility of a male and the frequency of cells with multivalent configurations among his diakinesis-metaphase I cells. We interpreted this to confirm that the length of translocated chromosome segments has some influence on the proportion of unbalanced gametes in the ejaculate, presumably reflecting the frequency with which adjacent-1 and adjacent-1 segregations and 3-1 misdivisions occur.

Animals↗
PubMed1980

Repair in fertilized eggs of mice and its role in the production of chromosomal aberrations.

The fertilized egg may influence the yield of dominant-lethal mutations produced from chemical treatment of male postmeiotic germ cells to a small or large extent depending upon the mutagen used and the competence of the egg to repair the premutational lesions induced. The strain of females has little influence on the yield of dominant-lethal mutations induced by triethylenemelamine or ethyl methane-sulfonate in spermatids and spermatozoa, but it has a large influence in the case of isopropyl methanesulfonate. In addition to this difference, triethylenemelamine and ethyl methanesulfonate induce high levels of heritable translocations at these germ cell stages whereas isopropyl methanesulfonate is practically ineffective, even though doses of these chemicals produced comparable levels of dominant-lethal mutations. These differences between ethyl methanesulfonate and triethylenemelamine on one hand and isopropyl methanesulfonate on the other were hypothesized to be a function of the types of chromosomal lesions present at the time of repair activity and whether or not chromosomal aberrations were already fixed at the time of postfertilization pronuclear DNA synthesis.

Animals↗
PubMed1980

Heritable translocation and dominant-lethal mutation induction with ethylene oxide in mice.

Ethylene oxide was studied for induction of dominant-lethal mutations and heritable translocations in male mice. The chemical was prepared in water and injected intraperitoneally. The dominant-lethal study was conducted using a single injection of 150 mg/kg (maximum tolerated dose); in the heritable translocation study males were injected daily on weekdays for 5 weeks with 60 or 30 mg/kg dose per day. Results clearly showed that ethylene oxide is effective in inducing dominant-lethal mutations and that the 4 stocks of untreated females used do not differ or may differ only slightly in the ability of their eggs to repair ethylene oxide-induced lesions in male germ cells. Increases in the frequencies of heritable translocations were also observed at the 2-dose levels. These frequencies did not deviate significantly from those expected on the basis of dose-square kinetics.

Animals↗
PubMed1980

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↗
PubMed1979

Genetic lesions induced by chemicals in spermatozoa and spermatids of mice are repaired in the egg.

Conclusive proof that the mouse egg is capable of carrying out repair of genetic lesions present in the male genome was obtained through dominant-lethal studies of chemically treated spermatozoa and spermatids and through cytological analysis of first-cleavage metaphases. The maximum difference in repair capability between stocks of females, found for isopropyl methanesulfonate treatment, was large; considerably smaller differences were found for ethyl methanesulfonate, triethylenemelamine, and benzo[a]pyrene treatments; and no difference was found for x-ray treatment.

Animals↗