Search PubMedSearch

Biomedical subjects

G Ficsor

Publications and source records attributed to G Ficsor.

At least 19 recordsLinked to original sources

Growth of Chinese hamster ovary (CHO) cells in the presence of MMC in low-serum medium.

Chinese hamster ovary (CHO-WBLT) cells growing in McCoy's 5a with 10% fetal bovine serum (FBS) were adapted to 0.5% FBS in CHO-1 Complete Media System, a serum-free medium from Ventrex. Cells in these two media were exposed to 10(-7) M and 10(-8) M mitomycin C (MMC) for 24 h. Comparison of cell growth over 10 days showed that cells in 0.5% serum proliferate, though at a slower rate than cells in 10% serum. Treatment with MMC revealed that at 10(-7) M, MMC is cytotoxic to cells to both the media; at 10(-8) M, MMC is non-cytotoxic to cells in both media.

Animals

Enhancing cervical cancer detection using nucleic acid hybridization and acetic acid tests.

Acetowhitening of abnormal cervical epithelium has been suggested as an indicator of increased cervical cancer risk. The presence of human papillomavirus (HPV) types 16, 18, 31, 33 and 35 may also indicate increased cervical cancer risk. Hence, tests that detect these two abnormal conditions may augment that Papanicolaou smear (Pap test) as predictors of cervical cancer risk. The cohort consisted of 145 women aged 14 to 47 (mean 21 years) attending health clinics. Thirty women (20.6 percent) showed acetowhitening of the cervical epithelium following exposure to vinegar of 4-percent acetic acid content. Fourteen (9.6 percent) had a positive Pap test and 13 (9 percent) carried a cervical HPV infection as determined by the commercially available ViraPap and ViraType nucleic acid tests. Statistical analysis of the data showed a positive correlation between Pap, ViraPap and acetic acid tests results. The acetic acid test and the nucleic acid tests were the sole positive tests for 21 (14.5 percent) and nine (6.2 percent) women, respectively. Four women with negative Pap results were infected with HPV types previously shown to have an association with cervical intraepithelial neoplasias, carcinoma in situ and cervical cancer. The authors have concluded that the acetic acid and nucleic acid tests detect women at risk for cervical cancer who would not have been detected by the Pap test alone.

Acetates

Sperm enzyme activity analysis of individual sperm for detection of heritable mutations in mammals.

Male mice were injected i.p. with 2.5 mg/kg mitomycin C, 100 mg/kg ethyl nitrosourea or saline and mated with untreated virgin females five weeks later. Sperm from 64 of the F1 male progeny were analyzed histochemically for acrosin, succinic dehydrogenase and alpha-glycerophosphate dehydrogenase activity. The frequency of F1 males with sub-normal sperm enzyme activity was significantly higher among progeny from treated males than in controls. These results show that analysis of sperm enzyme activity in F1 males is a practical method for detection of transmitted mutations induced in a treated parent.

Acrosin

Comparison of behaviors for detection of heritable mutations.

Groups of five male HA (ICR) mice were injected intraperitoneally with 60, 150, 300, or 600 mg/kg body weight of ethyl methanesulfonate (EMS) or with saline vehicle. Each male was mated to two untreated females at 2 and 5 weeks after treatment. The two successive matings utilized sperm derived from post- and pre-meiotic germ cells, respectively. Progeny were evaluated for litter size, body weight, negative geotactic response, swimming patterns, limb use while swimming, water escape time, and open-field motor coordination activity. Body weight, geotactic response, limb use, and open-field behavior test results demonstrated that EMS causes heritable behavior mutations in both post- and pre-meiotic germ cells. Among the tests that showed inherited differences between control and treated groups, the computer-monitored open-field behavior test was the most definitive.

Animals

Ethylnitrosourea treatment increases lectin binding to mouse germ cells.

Germ cell toxicity was assessed by investigating the binding of FITC-labeled lectins to mouse testis cells before and 18 days after treatment with ethylnitrosourea (ENU). Flow cytometry of testis cells dual-labeled with FITC-lectin plus the DNA stain, propidium iodide, allowed analysis of haploid (1C), diploid (2C), and dividing (4C) cell populations. Soybean agglutinin, wheat germ agglutinin, concanavalin A and Limax flavus agglutinin bound to normal mouse testis cells containing 1C, 2C or 4C DNA. Asparagus pea lectin and Bandeireae simplicifolia I isolectin B4 did not. ENU treatment reduced the number of testis cells and increased lectin binding, particularly of those lectins which bound to untreated cells.

Animals

Comparison of methods for detecting mitomycin C- and ethyl nitrosourea-induced germ cell damage in mice: sperm enzyme activities, sperm motility, and testis weight.

Testes weights, sperm motility and enzyme activities in single sperm were compared with respect to their ability to detect either developmental or mutational damage to germ cells. Male mice were injected i.p. with 2.5 mg/kg mitomycin C (MC) or 50 or 100 mg/kg ethylnitrosourea (ENU) or saline and were then killed at times such that sperm derived from treated vas sperm (SZ), spermatids (ST), preleptotene-late-spermatogonial cells (PLSG), spermatogonial cells (SG), or spermatogonial stem cells (SGS) could be evaluated. Testis weights decreased significantly as early as 1 wk after treatment, with the greatest decrease reached 3-4 wk after treatment, followed by recovery to normal levels 10-15 wk after treatment. We conclude that testis weight, which is easily obtained, is a sensitive indicator of germ cell damage by these agents. Sperm from each animal were evaluated for sperm motility, acrosin activity, succinic dehydrogenase (SDH) activity with or without the competitive inhibitor malonate or after exposure to 60 degrees C for 10 min. The latter two assays were to detect sperm enzymes resistant to the inhibitor or heat. The presence of the acrosin protein was also detected immunologically. Sperm motility decreased most from treatment of PLSG and SG. After MC or ENU treatment, the greatest loss of acrosin activity and of the acrosin protein was also noted in sperm derived from treated PLSG and SG. MC and ENU failed to induce SDH activity in single sperm resistant to 60 degrees C heat inhibition or to inhibition by malonate. Of the sperm assays, acrosin activity proved to be the most sensitive indicator of germ cell damage and was the simplest to measure.

Acrosin

Cytochemical detection of hyaluronidase activity in single human and mouse sperm by an improved substrate-film technique.

A substrate-film method is described that allows the detection of hyaluronidase activity in nearly 100% of single human and mouse sperm. The level of hyaluronidase activity as determined by halo diameters was greater in mouse than in human sperm. This simple method may have use as a screening method for identifying compounds that cause developmental or genetic defects in male germ cells, or for the diagnosis of infertility due to decreased hyaluronidase activity.

Animals

Histochemical evaluation of sodium aurothiomalate inhibition of mouse sperm enzymes.

Histochemical procedures for the mouse sperm enzymes hyaluronidase, esterase and acrosin were used to test the inhibitory effects of the low molecular weight hyaluronidase inhibitor sodium aurothiomalate (Myocrisin): hyaluronidase and esterase, but not acrosin, were inhibited. These enzymes were also inhibited in testis homogenates when assayed spectrophotometrically. These results suggest that the antifertility effects of sodium aurothiomalate may be due to the inhibition of several sperm enzymes including both hyaluronidase and esterase. These histochemical assays may be useful for in-vivo detection of chemicals that affect male fertility.

Acrosin

Testes weight reflect ethylnitrosourea induced histopathology in mice.

The powerful mutagen/carcinogen ethylnitrosourea (ENU) decreases testis weight in mice. A histopathological cause was determined for this effect. Groups of 3 mice were injected with 0, 50, 100 or 200 mg ENU/kg b.w. and were killed 1, 2, 4, 5, 7, 9, 13 or 15 weeks later. Microscopic examination of PAS-hematoxylin-stained sections showed a dose-and-time-dependent loss of germ cells from the seminiferous tubules 1-7 weeks after treatment followed by recovery from the damage. Testis weight decrease and recovery followed a similar course.

Animals

Gelatin-substrate film technique for detection of acrosin in single mammalian sperm.

Sperm acrosin proteolytic activity in single sperm can be detected by a protein-free halo on a gelatin-substrate film. With current techniques, halos have variable sizes and are often absent because of unevenness of the hand-spread gelatin-substrate film. We prepared gelatin-substrate films with a coating machine. Using these films, halos were formed uniformly throughout the gelatin-substrate films in the vicinity of single mammalian sperm. The level of acrosin activity as determined by halo diameters was human greater than dog greater than squirrel monkey greater than mouse greater than rat. This simple and reproducible technique may be used to diagnose infertility due to decreased acrosin activity, as a screening method for identifying compounds with male sterility effects, and for identifying agents with developmental and/or genetic effects.

Acrosin

Germ cell-specific decrease of acrosomal proteolytic activity, sperm motility, and number in mitomycin C-treated mice.

Assessment of mammalian sperm acrosomal proteolytic activity, sperm motility, and sperm count may be useful for detecting mutagens, carcinogens, developmentally active agents, and antifertility effects. Groups of six albino mice were given a single i.p. injection of 5 mg/kg mitomycin C (MC) or saline. One treated and one control group of mice were killed 1, 3, 5, 7, or 10 weeks later. Sperm extracted from the vasa deferentia at these killing times were derived from cells treated as spermatozoa, spermatids, preleptotene-late spermatogonial cells, spermatogonial cells, and spermatogonial stem cells. In sperm derived from treated preleptotene or spermatogonial cells, the sperm count, sperm motility, and acrosomal proteolytic activity were decreased significantly. Acrosomal proteolytic activity was also decreased in sperm from spermatogonial stem cells. None of these sperm phenotypes were decreased in treated spermatozoa and spermatids. We propose the hypothesis that induced loss of sperm motility and acrosomal proteolytic activity in single spermatozoa derived from MC-treated spermatogonial cells is caused by mutational or developmental effects, whereas in preleptotene-derived and late-spermatogonium-derived sperm similar dysfunction results from developmental effects. Our data support the hypothesis indirectly. Since a low sperm count is correlated with decreased fertility and acrosomal proteolytic activity is essential for penetration of the zona pellucida by the sperm, the presence of these sperm phenotypes may help to detect chemicals with antifertility effects.

Acrosin

Mitomycin C- and streptozotocin-induced motility and numerical sperm variants in mice.

Groups of HA (ICR) albino male mice were injected once i.p. with o, 2.5 or 5.0 mg/kg mitomycin C (MC), or 2.65 or 26.5 mg/kg streptozotocin (SZ). 4 weeks after treatment each male was mated with 2 untreated CF1 albino females. 5 weeks after treatment the males were killed for determination of sperm motility and count from the cauda and vas. Both agents decreased sperm motility and count in a dose-dependent manner in the treated males. The effect is believed to be caused primarily by interference with gene expression involved in spermatogenesis. The females mated to treated males showed decreased percentage pregnancy and had few progeny. Mean percentage motility and sperm count was significantly lower in the F1 male progeny of MC- or SZ-treated males compared to control males. 50-60% of F1 males form treated male parents had percentage sperm motility below control range. Decreased motility and count in the F1 progeny of treated males may have been caused by gene mutations and/or chromosomal aberrations. The method which is presented may be useful for detecting mutations and/or developmental effects.

Animals

Rhesus monkey (Macaca mulatta) model in genetic toxicology mitomycin C clastogenicity in germ cells.

The value of rhesus monkeys (Macaca mulatta) as a genetic toxicology model is limited by their scarcity, expense, and impracticality of progeny testing. However, in some special circumstances, e.g., accidental exposure of humans to potential mutagens, rhesus monkeys or other primates may provide a superior animal model to help to cope with a difficult public health situation. Using the testis as a target organ we found that when primary spermatocytes were treated in pre-leptotene stage with 1 mg mitomycin C/kg body weight, the frequency of exchanges, fragments, sex-chromosome and autosomal univalents increased significantly at diakinesis-metaphase I. This response was absent in cells treated during diplotene, late pachytene or during spermatogonial stages. We suggested that animals should be evaluated not only for genetic toxicology parameters, but also toxicologically, histologically, behaviorally, for carcinogenesis and seminal cytology. Whenever possible, the animals should be recycled.

Animals

Bone marrow and lymphocyte cytogenetics of rhesus monkeys (Macaca mulatta) treated with the clastogen Mitomycin C.

Rhesus monkeys (Macaca mulatta) were used to determine their effectiveness as experimental animals for different cytogenetic tests with mitomycin C (MC). The micronucleus test (MNT and/or chromosome analysis of blood and bone marrow were made before and/or after the treatment with mitomycin C. Thus, the controls data and treated data were obtained from the same animals. With the employed methology, the micronucleus test could not be performed on living animals. Less chromosomal damage was detected in the micronucleus test of post-mortem samples than in the chromosome analysis of bone marrow. No influence by the mutagen could be observed in lymphocyte chromosomes at any of the different times of analysis. In contrast to this, bone-marrow chromosomes seemed to be highly affected by mitomycin C at day 1, 2 and 3 after injection. However, before treatment and at day 14, 16 and 17 after treatment there was no visible increase in chromosomal aberration in bone marrow.

Animals