Possible modulating action of plant infusion of Ocimum sanctum L. on chromosomal aberrations and sister chromatid exchanges induced by chlormadinone acetate in human lymphocytes in vitro.

Chlormadinone acetate (CMA) is a synthetic progesterone analogue. It has its usage in oral contraceptives formulations and also for estrous synchronization of animals. The aim of the present study is to study the anti- genotoxic activity of the plant infusion against the CMA induced genotoxic damage on cultured human lymphocytes, using chromosomal aberrations and sister chromatid exchanges (SCFs) as parameters. For chromosomal aberration analysis, the treatment of 40 microM of CMA was associated with 4.33% abnormal metaphases. The treatment of 40 microM of CMA, separately with 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) gm l(-1) of plant infusion results in the reduction of the number of abnormal metaphases i.e. 2.67%, 2.00% and 1.67% respectively. For sister chromatid exchange analysis, the frequency of sister chromatid exchange per cell (SCE(S)/Cell) for the treatment of 40 microM of CMA was 6.43. The treatment of 40 microM of CMA, separately with 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) gm l(-1) of plant infusion results in the significant reduction of the frequency of SCE(S)/Cell i.e. 3.76, 3.01 and 2.94, respectively, as compared to the CMA (40 microM) treatment alone (6.43). The used dosages of plant infusion did not increase chromosomal aberrations and sister chromatid exchanges at significant level as compared to the untreated. The results of the present study suggest that the plant infusion per se does not have genotoxic potential, but can modulate the genotoxicity of chlormadinone acetate in human lymphocytes in vitro.

The Effects of Etodolac, Nimesulid and Naproxen Sodium on the Frequency of Sister Chromatid Exchange after Enclused Third Molars Surgery

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAID) are frequently used in oral surgical procedures in dentistry. The evaluation of the frequency of sister chromatid exchange (SCE) is accepted as a reliable cytogenetic method to assess the genotoxic effects of environmental factors. MATERIALS AND METHODS: In this study, the genotoxic effects of various NSAIDs were assessed in 30 patients to who they were administered following encluosed third molar surgery using SCE analysis before and after the operation. The frequency of SCE was evaluated before the operation and after 3 days of etodolac, nimesulid and naproxen use. RESULTS: There was no statistically significant difference in the frequency of SCE between the preoperative and postoperative states in patients given etodolac, nimesulid or naproxen sodium. CONCLUSION: Short term use of selective and non-selective NSAIDs was not associated with a significant genotoxic effect that could be detected using the SCE method in peripheric lymphocytes.

Protective role of nordihydroguaiaretic acid (NDGA) against the genotoxic damage induced by ethynodiol diacetate in human lymphocytes in vitro.

Antioxidants and plant products are reported to reduce the genotoxic damage of steroids. In our present study we have tested different dosages of nordihydroguaiaretic acid (NDGA) against the genotoxic damage induced by ethynodiol diacetate in the presence of S9 mix. Treatments with nordihydroguaiaretic acid (NDGA) results in the reduction of the genotoxic damage. A significant decrease was observed at all the tested doses of NDGA in sister chromatic exchanges of number of abnormal cells. The results suggest a protective role of NDGA against the genotoxic damage.

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.

Sister-chromatid exchange analysis on long-term benzathine penicillin for secondary prophylaxis of rheumatic fever.

A single intra-muscular injection of 1.2 millions units of benzathine penicillin every 4 weeks is the most widely used method for the antibiotic prophylaxis of rheumatic fever. The aim of this study is to evaluate the effect of long-term benzathine penicillin on DNA in patients with rheumatic fever. Thirty children with confirmed rheumatic fever who were on the benzathine penicillin prophylaxis were enrolled in the study, and 30 similar normal children served as a control group. To detect any DNA damage, SCE analysis were performed in circulating lymphocytes of the subjects. A statistically significant increased frequency of SCE was observed in children on the benzathine penicillin prophylaxis (no = 30, mean SCEs/cell +/- SD 7.54 +/- 1.81) as compared to a control group (no = 30, mean SCEs/cell +/- SD 5.82 +/- 1.40). It has been suggested that the difference in the SCE frequencies was induced by the administration of the benzathine penicillin for a long time, and further investigations are needed to confirm this toxic effect.

Adaptive response to low dose of EMS or MMS in human peripheral blood lymphocytes.

Human peripheral blood lymphocytes stimulated in vitro for 6 hr were exposed to a low (conditioning) dose of ethyl methanesulfonate (EMS; 1.5 x 10(-4) M) or methyl methanesulfonate (MMS; 1.5 x 10(-5) M). After 6 hr, the cells were treated with a high (challenging) concentration of the same agent (1.5 x 10(-3) M EMS or 1.5 x 10(-4) M MMS). The cells that received both conditioning and challenging doses became less sensitive to the induction of sister chromatid exchanges (SCEs) than those which did not receive the pretreatment with EMS or MMS. They responded with lower frequencies of SCEs. This suggests that conditioning dose of EMS or MMS has offered the lymphocytes to have decreased SCEs. This led to the realization that pre-exposure of lymphocytes to low dose can cause the induction of repair activity. This is a clear indication of the existence of adaptive response induced by alkylating agents whether it is ethylating or methylating in human lymphocytes in vitro.

Protein phosphatase-1 inhibition induces high SCEs in normal whole blood cultures.

Effect of 1,25,50 and 75 nM of okadaic acid (OA) on human lymphocytes from healthy individuals in culture has been investigated. To our surprise, we observed induction of significantly high sister chromatid exchanges (SCEs) at concentrations known to inhibit both protein phosphatase-1 (PP-1) and protein phosphatase -2A (PP-2A). However, 1 nM okadaic acid, known to inhibit PP-2A alone, did not induce this cellular feature/phenotype. This novel preliminary observation lays foundation for investigating further the role of PP-1 inhibition in governing as yet unknown finer controls in the induction of high SCEs, the mechanism for which has eluded answers till date.

Induction of sister chromatid exchanges in phenytoin treated & untreated patients with epilepsy.

The mutagenic potential of phenytoin (PHT) was studied using the sister chromatid exchange (SCE) assay. Twenty nine PHT treated epileptics, 32 untreated and 32 normal healthy controls were analysed. Similar SCE frequencies were observed in untreated patients and patients on PHT monotherapy. Both groups had significantly increased SCE frequency as compared to controls. No positive correlation of SCE frequency with sex and duration of therapy was observed. The results of the present study suggest the role of the disease condition in inducing genetic damage as assessed by increased SCE frequencies.

In vivo sister chromatid differentiation and baseline sister chromatid exchanges in a mouse ascites tumour model.

Induction of differentially stained sister chromatids at G2/M and determination of baseline sister chromatid exchanges (SCEs) in ascites form of mouse sarcoma 180 cell line have been done by in vivo incorporation of 5-bromodeoxyuridine (BrdU) for two consecutive DNA replication cycles. The baseline SCE frequency is 6.24 at log phase of tumour growth.

Sister chromatid exchanges [sces] in mice exposed to benzene

The study aimed to evaluate the cytotoxic and cytogenetic effects of benzene exposure on mice. Swiss Webster and BDFI mice were subjected to intraperitoneal [ip] injections of benzene at the concentrations of 2.6, 3.2, 4.6, 12.8 and 25.6 m.mol/kg. The effect of increasing benzene concentrations on cell division and sister chromatied exchanges [SCEs] induction in bone marrow and alveolar macrophages of intact mice and regenerating liver cells of hepatectomized mice were studied. The results showed clear dose response relationships in all cell types. No significant differences in SCEs frequencies were observed either among the three cell types or between Swiss Webster and BDFI mice. The hepatectomized Swiss Webster mice showed higher frequencies of SCEs than the intact mice however, the difference was statistically significant only at the concentration of 25.6 m.mol/kg. no significant increase in SCEs frequencies and benzene exposure at the beginning of the first cell cycle. Exposure of the mice to benzene for 4 successive days at the concentrations of 3.2 and 6.4 m.mol/kg respectively did not show significant increase in SCEs frequencies than that induced following single benzene exposure at the same concentrations. The average percentage of the second division metaphases showed appreciable reduction only at the concentration of 25.6 m.mol/kg. Hepatectomy failed to alter the cytotoxicity of benzene as evidenced by lack of reduction of second division cells of the exposed mice relative to the controls

Sister chromatid exchange in mutagenicity testing: a study of mercapto oxazolyl carboxylic acid

As trocas entre cromátides irmäs (TCI) e o ciclo celular foram estudados por meio da técnica BrdU-Giemsa para avaliar a sua capacidade e sensibilidade de detecçäo de efeitos tóxicos, particularmente os mutagênicos e/ou carcinogênicos. Foi utilizada uma substância clastogênica - o ácido mercapto oxazolil carboxílico, uma droga anti-reumática - para avaliar seu efeito "in vitro" quanto a induçäo de (TCI), aberraçöes cromossômicas e quanto ao ciclo celular. Foi verificado que esta droga induziu um aumento na freqüência de (TCI) em concentraçöes inferiores àquelas que produziram um aumento na freqüência de aberraçöes cromossômicas. A droga, nas concentraçöes mais baixas utilizadas, provocou uma antecipaçäo do ciclo celular enquanto que na concentraçäo mais elevada produziu um atraso deste. Assim, a avaliaçäo das (TCI) e do ciclo celular configura-se como um método potente e sensível no estudo da mutagenicidade e toxicidade de drogas

Cytogenetic Effects on Mouse Fetus of Acute and Chronic Transplacental In Vivo Exposure to Carbon Monoxide: Induction of Micronuclei and Sister Chromatid Exchanges

Carbon monoxide gas is found in the atmosphere whenever society has become industrialized. In addition to the fact that Korea has become industrialized, bituminous coal is used to heat homes here, in heating systems that, if not very carefully maintained, leak this gas, resulting in a number of deaths and near deaths each winter. It has only rarely been reported by investigators that genetic damage may be done transplacentally to a human fetus by a pregnant woman's being poisoned by CO. We explored this by evaluating the damage done to the mouse fetus through an in vivo experiment, using micronucleus and sister chromatid exchange (SCE) tests. Mice were mated and pregnant ones divided into a group that received acute exposures on 3 different days, a group that received chronic exposure, and a control group. In the meantime in the control group the incidence of both micronuclei and SCE was less on the maternal side, in both the acute and chronic exposure groups, whereas the incidences of both micronuclei and SCE were more on the maternal side. However, the incidence on the fetal side was not far behind. Increasing, the dosage of carbon monoxide with gestational age increased the incidence of both micronuclei and SCE in the mother and fetus alike.