An Evaluation of Genotoxicity Tests With Aquateric® Aqueous Enteric Coating

1999 ◽  
Vol 18 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Kathryn J. Batt ◽  
Lois A. Kotkoskie

The genotoxic potential of Aquateric® Aqueous Enteric Coating was evaluated in the Ames test, the mouse lymphoma mutation assay, and the mouse micronucleus test. Aquateric was not mu-tagenic when tested in Salmonella typhimurium cell strains TA98, TA100, TA1535, TA1537, TA1538, with or without metabolic activation. A mouse lymphoma assay was conducted at concentrations ranging from 116 to 2000 μg/ml and 116 to 1250 μg/ml in the absence and presence of metabolic activation, respectively. No increased mutant frequencies were noted for any concentration tested. Aquateric was tested in the mouse micronucleus assay at a single oral dose of 7200 mg/kg Aquateric (equivalent to 5000 mg/kg cellulose acetate phthalate, the major ingredient) and bone marrow was harvested at 24, 48, and 72 hours after treatment. There was no significant increase in the number of mouse bone marrow mi-cronucleated polychromatic erythrocytes in Aquateric-treated animals at any of the harvest times. Based on the negative results in the Ames test, the mouse lymphoma mutation assay, and the mouse micronucleus test, it was concluded that Aquateric is not genotoxic.

2009 ◽  
Vol 25 (1) ◽  
pp. 5-13
Author(s):  
DJ Oakes ◽  
HE Ritchie ◽  
PDC Woodman ◽  
E Narup ◽  
M Moscova ◽  
...  

The Royal Australian Air Force (RAAF) has reported that personnel involved in F-111 fuel tank maintenance were concerned that exposure to a range of chemicals during the period 1977 to mid-1990s was the cause of health problems, including cancer. Particular concern was directed at SR-51®, a desealant chemical mixture containing the following four solvents: aromatic 150 solvent (Aro150), dimethylacetamide, thiophenol (TP), and triethylphosphate. The present study examined the mutagenic potential of SR-51® using a range of well-known mutagen and genotoxin assays. The tests used were i) a modified version of the Ames test, ii) the mouse lymphoma assay, iii) the comet assay (a single-cell gel electrophoresis assay), and iv) a mouse micronucleus test. The modified Ames test used mixed bacterial strains in liquid suspension media. The Ames test results showed that SR-51® (tested up to the cytotoxic concentration of 36 μg/ml, 30 min incubation) in the presence and absence of S9 metabolic activation was not mutagenic. The mouse lymphoma assay used cultured mouse lymphoma cells in a microwell suspension method. The mouse lymphoma assay was also negative with SR-51® (tested up to the cytotoxic concentration of 22.5 μg/ml, 3 h incubation) in the presence and absence of S9 metabolic activation. The Comet assay, using cultured mouse lymphoma cells, showed no evidence of DNA damage in cells exposed up to the cytotoxic concentration of SR-51® at 11.25 μg/ml. The in-vivo mouse micronucleus test was undertaken in wild-type C57Bl6J male mice dosed orally with SR-51® for 14 days with a single daily dose up to 360 mg/kg/day (the maximum-tolerated dose). No increases were observed in micronuclei (MN) frequency in bone marrow collected (24 h after final dose) from SR-51®-treated mice compared to the number of MN observed in bone marrow collected from untreated mice. Tissues collected from treated mice at necropsy demonstrated a significant increase in spleen weights in the high dose mice. Gas chromatography analysis of SR-51® identified more than 40 individual components and an oxidation product, diphenyldisulfide derived from TP under conditions of mild heating. In conclusion, there was no evidence that SR-51® is mutagenic.


1993 ◽  
Vol 12 (2) ◽  
pp. 155-159 ◽  
Author(s):  
B. Bhaskar Gollapudi ◽  
V. A. Linscombe ◽  
M. L. Mcclintock ◽  
A. K. Sinha ◽  
C. R. Stack

DGBE was evaluated in a forward gene mutation assay at the HGPRT locus of CHO cells in culture and in an in vivo mouse bone marrow micronucleus test for cytogenetic damage. DGBE did not elicit a positive response in the CHO/HGPRT assay when tested up to a maximum concentration of 5000 μg/ml with and without an external metabolic activation system (S-9). In the micronucleus test employing three post-treatment bone marrow sampling times (24, 48, and 72 hr), DGBE was ineffective in increasing the incidence of micronucleated polychromatic erythrocytes (MN-PCE) when tested in both sexes up to a maximum tolerated dose of 3300 mg/kg body weight. Thus, these data and those of others indicate a general lack of genotoxic potential for DGBE in short-term tests.


Author(s):  
Kunjumon Dayana ◽  
Megaravalli R. Manasa

Background: Genotoxicity screening of drugs is essential. It is mandatory for new drugs. However, screening of drugs already in use is also necessary. Several cephalosporins are reported to induce chromosomal aberrations in previous studies. But there is paucity of data regarding the genotoxic potential of ceftriaxone. Hence the present study was undertaken to evaluate the genotoxic potential of ceftriaxone, a third generation cephalosporin, by micronucleus assay in albino mice.Methods: In vivo micronucleus test was performed with mice bone marrow after intraperitoneal injection of ceftriaxone at 100mg/kg BW and 200mg/kg BW at 24 hr and 48 hr harvest time. Mice bone marrow was harvested, and slides were prepared. The percentage of micronucleated polychromatic erythrocytes (% MnPCE) and the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE:NCE) were determined. The data from ceftriaxone treated groups was compared with control group and analyzed using ANOVA followed by Dunnett's test.Results: Ceftriaxone at the dose of 100mg/kg BW and 200mg/kg BW did not exhibit any significant increase in the percentage of micronucleated polychromatic erythrocytes. It also did not decrease the ratio of polychromatic erythrocytes to normochromatic erythrocytes significantly.Conclusions: The present study demonstrates that ceftriaxone is not genotoxic in in vivo micronucleus study in albino mice at a dose of 100mg/kg BW and 200mg/kg BW.


2017 ◽  
Vol 78 (1) ◽  
pp. 1-12
Author(s):  
M. F. G. Boriollo ◽  
T. A. Silva ◽  
M. F. Rodrigues-Netto ◽  
J. J. Silva ◽  
M. B. Marques ◽  
...  

Abstract Handroanthus impetiginosus has long been used in traditional medicine and various studies have determined the presence of bioactive chemical compounds and potential phytotherapeutics. In this study, the genotoxicity of the lyophilized tincture of H. impetiginosus bark (THI) was evaluated in mouse bone marrow using micronucleus assays. The interaction between THI and genotoxic effects induced by the chemotherapeutic agent, doxorubicin (DXR), was also analyzed. Experimental groups were evaluated 24 to 48 h after treatment with N-nitroso-N-ethylurea (NEU; 50 mg/kg), DXR (5 mg/kg), sodium chloride (NaCl; 150 mM), and THI (0.5-2 g/kg). Antigenotoxic assays were carried out using THI (0.5 g/kg) in combination with NEU or DXR. Analysis of the micronucleated polychromatic erythrocytes (MNPCEs) indicated no significant differences between treatment doses of THI (0.5-2 g/kg) and NaCl. Polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) ratios did not indicate any statistical differences between DXR and THI or NaCl, but there were differences between THI and NaCl. A significant reduction in MNPCEs and PCE/NCE ratios was observed when THI was administered in combination with DXR. This study suggested the absence of THI genotoxicity that was dose-, time-, and gender-independent and the presence of moderate systemic toxicity that was dose-independent, but time- and gender-dependent. The combination of THI and DXR also suggested antigenotoxic effects, indicating that THI reduced genotoxic effects induced by chemotherapeutic agents.


2005 ◽  
Vol 24 (6) ◽  
pp. 427-434 ◽  
Author(s):  
Gunda Reddy ◽  
Gregory L. Erexson ◽  
Maria A. Cifone ◽  
Michael A. Major ◽  
Glenn J. Leach

Hexahydro-1,3,5-trinitro-1,3,5-triazine, a polynitramine compound, commonly known as RDX, has been used as an explosive in military munitions formulations since World War II. There is considerable data available regarding the toxicity and carcinogenicity of RDX. It has been classified as a possible carcinogen (U.S. Environmental Protection Agency, Integrated Risk Information System, 2005, www.epa.gov/IRIS/subst/0313.htm ). In order to better understand its gentoxic potential, the authors conducted the in vitro mouse lymphoma forward mutation and the in vivo mouse bone marrow micronucleus assays. Pure RDX (99.99%) at concentrations ranging from 3.93 to 500 μg/ml showed no cytotoxicity and no mutagenicity in forward mutations at the thymidine kinase (TK) locus in L5178Y mouse lymphoma cells, with and without metabolic activation. This finding was also confirmed by repeat assays under identical conditions. In addition, RDX did not induce micronuclei in mouse bone marrow cells when tested to the maximum tolerated dose of 250 mg/kg in male mice. These results show that RDX was not mutagenic in these in vitro and in vivo mammalian systems.


2012 ◽  
Vol 40 (05) ◽  
pp. 1019-1032 ◽  
Author(s):  
Chang Keun Kang ◽  
Dae Sik Hah ◽  
Chung Hui Kim ◽  
Euikyung Kim ◽  
Jong Shu Kim

The present study was conducted to evaluate the activity of methanol extracts from Houttuynia cordata Thunb. (HC) in a reverse mutation assay in Salmonella typhimurium, and a chromosome aberration assay in the Chinese hamster ovary (CHO) cell line and to evaluate its effect on the occurrence of polychromatic erythrocytes in mice. In the reverse mutation assay using Salmonella typhimurium TA98, TA100, TA1535, and TA1537 and Escherichia coli WP2urvA-, methanol extracts of HC (5, 2.5, 1.25, 0.62, or 0.312 mg/plate) did not induce reverse mutations in the presence or absence of an S9 metabolic activation mixture. In the chromosome aberration test using CHO cells, methanol extracts (1.25, 2.5 or 5 μg/ml) caused a few incidences of structural and numerical aberrations, in both of absence or presence of an S9 metabolic activation mixture, but in comparison with the positive control group, these incidences were not significantly increased. In the mouse micronucleus test, no significant increases in the occurrence of micronucleated polychromatic erythrocytes were observed in male ICR mice that were orally administered methanol extracts of HC at doses of 2.0, 1.0, or 0.5 g/kg. From these results, we concluded that the methanol extracts of HC did not induce harmful effects on genes in bacteria, a mammalian cell system or in mouse bone marrow cells. Thus, HC's use for health promotion and/or a sick remedy for humans may be safe.


2021 ◽  
Vol 11 (21) ◽  
pp. 10257
Author(s):  
Young-Jae Song ◽  
Dong-Gu Kim ◽  
Jeonghoon Lee ◽  
Wonnam Kim ◽  
Hyo-Jin An ◽  
...  

The various species that comprise the genus Glycyrrhiza (Licorice) have long been used as oriental herbal medicines in Asian countries. Wongam (WG), which is a new variety of Glycyrrhiza, was developed in Korea to overcome the limitations of low productivity, environmental restrictions, and an insufficient presence of glycyrrhizic acid and liquiritigenin. In this study, we evaluated WG extract’s genotoxicity through an in vitro bacterial reverse mutation (AMES) test, an in vitro chromosome aberration test, and an in vivo mouse bone marrow micronucleus test. In the AMES test, WG extract at concentrations of up to 5000 µg/plate showed no genotoxicity regardless of S9 mix. No chromosome aberrations appeared after 6 h in 1400 µg/mL WG extract regardless of S9 mix or in 1100 µg/mL WG extract after 24 h without S9 mix. Nor was there a significant increase in the number of micronucleated polychromatic erythrocytes to total erythrocytes up to 5000 mg/kg/day for 2 days detected in the micronucleus test. These results confirm that WG extract is safe for use as an herbal medicine, as it precipitates no detectable genotoxic effects.


2013 ◽  
Vol 85 (2) ◽  
pp. 737-744 ◽  
Author(s):  
MONICA B.B. BELLE ◽  
DANIELA D. LEFFA ◽  
DALIANE MAZZORANA ◽  
VANESSA M. DE ANDRADE

Contrast media (CM) are frequently used in diagnostic radiology and in radiotherapy as a diagnostic tool and in treatment planning. Previous studies have demonstrated that these compounds induce chromosomal aberrations. This study evaluates the mutagenic effects induced by the contrast medium Urografina® 292 (meglumine amidotrizoate and sodium-ionic dimmer) in bone marrow cells (BMC) of mice in vivo. Micronuclei assay was performed in BMC of CF-1 mice injected with CM 1.5 and 3.0 mL/kg intravenous doses and 1.0, 2.0, 3.0 mL/kg intraperitoneal doses. The animals were beheaded 24 h after treatment by cervical dislocation, and femur BMC from each animal were used in the micronucleus test. The group treated with the highest intravenous injection of Urografina® 292 (3.0 mL/kg) presented an increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in relation at the control group (P<0.05). The results obtained after intraperitoneal administration of CM showed that all doses (1.0 mL/kg, 2.0 mL/kg and 3.0 mL/kg) increased the frequency of MNPCEs, being significantly different from the negative control (P< 0.01). The present results suggest that iodinated contrast media Urografina® 292 may cause a significant increase of cytogenetic damage in bone marrow cells of mice.


PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0137063 ◽  
Author(s):  
Carolina Ribeiro e Silva ◽  
Flávio Fernandes Veloso Borges ◽  
Aline Bernardes ◽  
Caridad Noda Perez ◽  
Daniela de Melo e Silva ◽  
...  

2015 ◽  
Vol 8 (4) ◽  
pp. 184-192 ◽  
Author(s):  
Ifeoluwa Temitayo Oyeyemi ◽  
Olaide Maruf Yekeen ◽  
Paul Olayinka Odusina ◽  
Taiwo Mary Ologun ◽  
Orezimena Michelle Ogbaide ◽  
...  

Abstract Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS.


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