Effect of famciclovir on the testes, sperms and chromosomes of albino rates; histological and cytogenetic study

Famciclovir is a widely used antiviral drug it has a potent and selective inhibitory effect on many human herpes viruses. Some side effects to the drug were reported by the Food and Drug Administration. The aim of this study was to evaluate the histological effect of maximum therapeutic dose of famciclovir, antiviral drug, on the testes, sperms and chromosomes of albino rats. Forty male albino rats have been divided into four groups, ten rats for each. The first was served as a control group; the second was treated for 2 weeks with 135 mg/ kg b. w.t./ day. The third was treated for 4 weeks with the same dose; and the forth group was served as recovery group, where the animals were examined 4 weeks after stopping the drug. Rats were decapitate and testes specimens were taken and stained with Haematoxylin and Eosin. The sperms were examined for number, viability, motility and shape abnormalities. For chromosomal study, rats from each group were anaesthetized and the bone marrow cells were obtained by Rabello-Gay and Ahmed method. Microscopic examination of the testicular specimens, revealed, disorganized germinal epithelium with abnormal mitotic figures and apoptotic cells. Sperm analysis showed that sperm count, viability and motility were decreased and the sperm anomalies were increased. Chromosomal analysis of bone marrow cells showed many aberrations as chromosomal fragments, terminal chromatid deletions, ring chromosomes, chromosomal gaps, dicentric chromosomes, clumping of the chromosomes and polyploidy. All the former results were time dependent and reversible. The maximum therapeutic dose of famciclovir affect spermatogenesis and alter normal sperm parameters. There were also chromosomal aberrations which are time dependent and reversible. So it is preferred to avoid the maximum therapeutic dose and prolonged intake of the drug

Anticlastogenic action of vitamin C against genotoxicity of estrogenic drug diethylstilbestrol (DES) in the human lymphocyte chromosomes.

Several sex steroids and estrogenic drugs are genotoxic in varying conditions and cause oxidative stress, which has been a field of interest to study the molecular mechanism of the genetic damage. Among the estrogenic drugs, a strong toxic effect is exerted by diethylstilbestrol (DES). In the present study it has been attempted to study its genotoxic effects in human lymphocyte assay system along with ameliorative or anticlastogenic effects of vitamin C. The drug was used with different dosage of concentrations on human lymphocytes administered in vitro. The parameters used were Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs). Higher levels of clastogeny and SCEs have been observed indicating significant damaging effect by the drug. Interesting ameliorating effects were observed in the presence of vitamin C which is a well-known antioxidant. The results support the possibility of practical application of natural protectors against the mutagenic/oenotoxic action of chemical mutagens.

Evaluation of the effect of steviol on chromosomal damage using micronucleus test in three laboratory animal species.

The chromosomal damage activity of steviol, a product of enzymatic alteration of stevioside, a natural non-caloric sweetener was reevaluated by using a bone marrow micronucleus test in both male and female hamsters, rats and mice. The micronucleus test is used widely as a rapid and efficient alternative in chromosome analysis for detecting in vivo cytogenetic damage. Steviol at the dose of 4 g/kg body weight for hamsters and 8 g/kg body weight for rats and mice showed no effect on the frequencies of micronucleus formation in bone marrow erythrocytes of both male and female hamsters, rats and mice. Moreover, there was also no apparent change in the PCEs:NCEs (polychromatic erythrocytes:normochromatic erythrocytes) ratio of the male animals of all three treated species at 24, 30, 48 and 72 hour intervals. However, steviol at the given dose can cause significant reduction of PCEs to NCEs ratio of the female hamsters at 72 hours and female rats and mice at 48 and 72 hours after receiving steviol orally. From these results, it could be proposed that steviol at the given dose to the treated animals produced adverse metabolites and these metabolites could reach the bone marrow, the target organ for micronucleus test. These metabolites also exhibited a slightly cytotoxic effect but not clastogenic effect to the bone marrow erythrocytes.

Olive oil protects against chromosomal aberrations induced by doxorubicin in wistar rat bone marrow cells

There is considerable interest in identifying dietary compounds which have the capacity to protect against chromosomal aberrations induced by antitumor agents. Fatty acids and their constituents are able to act as free radical scavengers. Doxorubicin (DXR) is an important chemotherapeutic agent, that also induces chromosome aberrations. Rat bone marrow cells treated simultaneously with olive oil (10 ml/kg body weight) and DXR (90 mg/kg body weight) developed significantly fewer chromosomal aberrations and abnormal metaphases than those treated with DXR alone.

Protective effect of butylated hydroxytoluene (BHT) against the clastogenic acitivity of cadmium chloride and potassium dichromate in hamster ovary cells

The effect of butylated hydroxytoluene (BHT), a widely used food additive, on chromosomal alterations induced by cadmium chloride (CC) and potassium dichromate (PD) in Chinese hamster ovary (CHO) cells was studied both at metaphase and anaphase-telophase. CHO cells were cultured for 15-16 h in the presence of PD (6.0, 9.0 or 12.0 mM), BHT (1.0 mg/ml), or PD plus BHT as well as CC (0.5, 1.0 and 2.0 mM), BHT or CC plus BHT for the analysis of chromosomal aberrations. To perform the anaphase-telophase test, cells were cultured in cover glasses and treated 8 h before fixation with the same chemicals. An extra dose of CC (4 mM) was used in this test. Both metal salts significantly increased chromosomal aberration frequencies in relation to untreated controls, and to DMSO- and BHT-treated cells. Post-treatment with BHT decreased the yield of chromosomal damage in relation to treatments performed with CC and PD. However, chromosomal aberration frequencies were significantly higher than those of the controls. In the anaphase-telophase test, CC significantly increased the yield of lagging chromosomes with the four doses employed and the frequency of lagging fragments with the highest dose. In combined treatments of CC and BHT, frequencies of the two types of alterations decreased significantly in relation to the cells treated with CC alone. No significant variation was found in the frequencies of chromatin bridges. Significant increases of numbers of chromatin bridges, lagging chromosomes and lagging fragments were found in cells treated with PD. The protective effect of BHT in combined treatments was evidenced by the significant decrease of chromatid bridges and lagging chromosomes in relation to PD-treated cells. Whereas BHT is able to induce chromosomal damage, it can also protect against oxidative damage induced by other genotoxicants.

Effect of chemical mutagenic agent on chromosomal pattern of Egyptian kwashiorkor infants

Previous animal studies suggested that malnutrition has a mutagenic and carcinogenic effect through inhibition of protein synthesis and DNA replication. However in humans, the effect of malnutrition is still controversial in spite of the fact that many studies had detected higher frequency of chromosomal aberrations in malnourished children as compared to the healthy controls. This work was carried out to determine the effect of malnutrition on human chromosomes and to test the cell sensitivity to chemical mutagens. We tried also to correlate the frequency of chromosomal damage to the level of plasma proteins. The study was conducted on twenty protein energy malnourished patients and twenty apparently healthy controls .Seventeen patients out of the twenty were reevaluated after nutritional rehabilitation and complete clinical recovery. Patients and controls were subjected to history taking, clinical examination, plasma protein electrophoresis and cytogenetic study. Cytogenetic study using micronucleus test [MN] revealed a statistically significant higher MN in patients before treatment [1.4 +/- 1.5] as compared to both after treatment [0.5 +/- 0.76] and the controls [0.55 +/- 1.0]. While there was no statistically significant difference in the frequency of MN in patients after treatment as compared to the controls. There was higher frequency of chromosomal aberrations [CA] in patients before treatment [3.2% +/- 2.49] as compared to patients after treatment [2% +/- 1.1] and the controls [2.3% +/- 2.8], however, this data was statistically insignificant [P>0.05]. There was negative correlation between total serum proteins and albumin and the frequency of chromosomal aberrations. Lymphocytes from malnourished patients were more susceptible to chromosomal damage induced by bleomycin in vitro than the lymphocytes of the control children. The detected susceptibility was significantly decreased after treatment of the patients. the mean percentage increase in CA [induced by blemoycin in vitro] was statistically higher in patients before treatment [199.6% +/- 199.6] as compared to after treatment [97% +/- 136.2] and the controls [102% +/- 160.4]

Effect of storage duration on cell cycle kinetics and yield of chromosomal aberrations in PHA-responsive human peripheral blood lymphocytes.

Phytohaemagglutinin (PHA)-responsive lymphocytes from human peripheral blood samples, either irradiated or un-irradiated, showed increased frequency of first division metaphase cells (detected by fluorescence plus Giemsa (FPG) staining) as a function of duration of storage. Irradiated and subsequently stored samples showed small but significant increase for the yield of dicentrics. The yield of aberrant metaphases and deletions (excess acentrics) remained unchanged. Increasing Bromodeoxyuridine (BrdU) concentrations slowed down the cell cycle progression but did not influence the yield of aberrations including that of dicentrics.

Relative ranking of culture media based on proliferation kinetics and spontaneous chromosomal aberrations in PHA-responsive human peripheral blood lymphocytes.

Proliferation kinetics and spontaneous yield of chromosomal aberrations phytohemagglutinin (PHA)-responsive peripheral blood lymphocytes were studied from blood samples collected from 45 individuals in 4 different synthetic media. Except for a significant difference for Eagle's MEM and RPMI 1640, the other media did not show difference for the yield of chromatid or chromosome type of aberrations. Differences were however noticed in the proliferation kinetics (mitotic and proliferative rate indices) of cells among the media used. The study indicated that (i) the intrinsic properties of media which influence proliferation rate and yield of chromosomal aberrations are independent of each other as higher proportion of first division cells do not correspond with higher frequency of chromosomal aberrations, (ii) the amount of free-radical scavengers present in the medium, apart from the genetic make-up of the individuals, may contribute to the spontaneous yield of chromosomal aberrations and (iii) RPMI 1640 medium, which showed higher transformation and faster cycling rate for the lymphocytes, may be considered as medium of choice for analysing two main cytogenetic end-points, chromosomal aberrations and sister chromatid exchanges (SCEs).

Post-metaphase mitotic events in cells treated with dinitrophenol.

The sequence of post-metaphase mitotic events, such as anaphase movement A and B, chromosome decondensation, nuclear envelope reformation and cytokinesis, has been studied in 2,4-initrophenol (DNP)-treated HeLa cells. The effects of DNP were found to be dose dependent and at concentrations higher than 3 mM, both anaphase A and B movements were totally and nearly instantaneously arrested. It could be shown that cytokinesis did not depend on the completion of anaphase movements. This was also true for nuclear envelope reformation which could take place even around condensed chromosomes arrested in anaphase. The post-metaphase mitotic events do not follow a strict causal sequence, but they can be dissociated from each other in anaphase-arrested cells.