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K T Cain

Publications and source records attributed to K T Cain.

At least 37 records · Page 2Linked to original sources

Exposure of female mice to ethylene oxide within hours after mating leads to fetal malformation and death.

When previously mated female mice were exposed to inhaled ethylene oxide at the time of fertilization of their eggs or during early pronuclear stage of the zygote (before DNA synthesis), a high incidence of mortality among conceptuses and of congenital abnormalities among both the dead and the surviving fetuses was observed. The developmental stage at which death occurred ranged from near the time of implantation to day 17 of gestation when examination of the uterine contents was performed. In comparison, midgestation and late fetal deaths were absent or minimal when the females were exposed either before mating or when conceptuses were in later zygotic stages (pronuclear DNA synthesis) or had reached the early two-cell stage. The random types of congenital abnormality observed and the remarkable stage-dependent sensitivity suggest a genetic basis for the response. The effects differ, both from genetic damages induced in premating germ cells, which lead only to death near the time of implantation, and from teratogenic damage, which leads to malformations only when exposure of embryos occurs during the period of major organogenesis.

Abnormalities, Drug-Induced↗

A balanced translocation in mice with a neurological defect.

A semisterile male translocation heterozygote [t(2; 14) 1Gso] that exhibited neurological symptoms and an inability to swim (diver) was found among the offspring of male mice treated with triethylenemelamine. All breeding and cytogenetic data showed a complete concordance between translocation heterozygosity and the neurological disorders. Homozygosity for the translocation seemed to be lethal at an early embryonic stage. Despite the distinctive neurologic symptoms, no anatomic or histological defects in either the ear or in the central nervous system were observed. Thus, a balanced chromosomal translocation can produce disease with an inheritance pattern that mimics a single dominant gene defect.

Animals↗

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↗

Tests for mutagenic effects of ammoniated glycyrrhizin, butylated hydroxytoluene, and gum Arabic in rodent germ cells.

Ammoniated glycyrrhizin, butylated hydroxytoluene, and gum Arabic are "generally recognized as safe" (GRAS) substances that are used primarily as additives in foods. These substances were incorporated into rodent diets and fed to male rats and mice for 10 and 8 wk, respectively. The treated male mice and rats were then tested for dominant lethal effects. The mice were also tested for induced heritable translocation. Results of the rat studies indicated a statistically significant dominant lethal effect of each of the compounds tested; however, the biological significance of this response is not known. Results of the mouse dominant lethal and heritable translocation studies, on the other hand, indicated no adverse effects of the compounds tested.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Relative rates at which dominant-lethal mutations and heritable translocations are induced by alkylating chemicals in postmeiotic male germ cells of mice.

There is a close relationship between the rates at which dominant lethal mutations and heritable translocations are induced by ethyl methanesulfonate (EMS) or triethylenemelamine (TEM) in male postmeiotic germ cells. This relationship does not hold for isopropyl methanesulfonate (IMS), which induced only negligible frequencies of heritable translocations at doses that induced high levels of dominant lethal mutations. Nor does IMS behave like EMS and TEM in the degree to which eggs of different stocks of females repair premutational lesions that are carried in the sperm-large differences between stocks for IMS treatment and small differences for EMS or TEM treatment. These dissimilarities between IMS and the other two alkylating chemicals are postulated to be attributable to differences in the types of lesions present at the time of repair activity and to whether or not chromosomal aberrations are already fixed prior to postfertilization pronuclear DNA synthesis.

Alkylating Agents↗