Sister-chromatid exchange and chromosome aberrations induced by paracetamol in vivo in bone-marrow cells of mice

Giri, Ashok K.; Sivam, Sheila; Khan, K.A.

doi:10.1016/s0165-1218(10)80004-7

Cited by 23 publications

(13 citation statements)

References 25 publications

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“…In mice dosed with paracetamol in vivo chromosome aberrations in bone marrow cells were demonstrated from a single dose of 200 mg/kg body weight and sister chromatid exchange from 50 mg/kg (Giri et al 1992), whereas 450 mg/ kg failed to induce micronuclei (King et al 1979). In agreement, prior glutathione depletion and 3-600 mg paracetamol per kg body weight were required to demonstrate covalent binding of NAPQI to DNA and strand breaks in mouse liver (Honglo et al 1994).…”

Section: Discussionmentioning

confidence: 92%

“…Despite the potent arylating capabilities and covalent binding to DNA neither NAPQI nor paracetamol are mutagenic in the usual test systems (Dybing et al 1984;Anonymous 1990) and the bulk of evidence do not support carcinogenicity (Anonymous 1990). Nevertheless, a number of genotoxic effects have been demonstrated in vivo and in vifro although the doses or concentrations required are rather high and may also cause other signs of toxicity (Dybing et al 1984;Anonymous 1990;Giri et al 1992;Hongslo et al 1994).…”

Section: Discussionmentioning

confidence: 99%

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Paracetamol‐Induced Spindle Disturbances in V79 Cells with and without Expression of Human CYP1A2

Jensen

Poulsen

Doehmer³

et al. 1996

Pharmacology & Toxicology

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Spindle disturbing effects in terms of c-mitosis and cytotoxicity of paracetamol were investigated in two Chinese hamster V79 cell lines, one of which (V79MZh1A2) was transfected with human CYP1A2. This enzyme catalyses the oxidative formation of the reactive paracetamol metabolite, NAPQI, believed to initiate hepatoxicity by covalent binding to proteins after overdose. In the native V79 cell line paracetamol increased c-mitosis frequency in a concentration dependent manner from 8.7 + or - 3.5% (control) to 66 + or - 18% at 20 mM. A significant increase to 13.3 + or - 3.5% was first seen at 2.5 mM in the native cell line (P<0.05). In the V79MZh1A2 cells the concentration-effect curve was slightly shifted to the left (P<0.05) with c-mitosis frequency increased to 12.1 + or - 2.6% (P<0.05) at 1 mM paracetamol. At 5 mM paracetamol the c-mitosis frequency was 14.4 + or - 5.0% and 19.0 + or - 3.8% in the native and CYP1A2 expressing cell lines, respectively (P<0.05). At 20 mM paracetamol the c-mitosis frequency was 61 + or - 10% in the V79MZh1A2 cells. Cell survival was reduced to approximately 50% at 5-10 mM paracetamol in both cell lines. At 20 mM paracetamol survival was further decreased to 39 + or - 9% in V79MZh1A2 cells only (P<0.05). The present study demonstrated that paracetamol may disturb the spindle of dividing cells conveying a risk of aneuploidy. The spindle disturbing effect was only slightly enhanced by expression of CYP1A2, suggesting that metabolic activation plays only a minor role in this genotoxic effect. The reduction of survival mirrored the increase in c-mitosis frequency.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Paracetamol‐Induced Spindle Disturbances in V79 Cells with and without Expression of Human CYP1A2

Jensen

Poulsen

Doehmer³

et al. 1996

Pharmacology & Toxicology

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“…The results indicated that paracetamol is a genotoxic drug in rats' bone marrow and spermatogonial cells as it increases chromosomal aberrations significantly. The genotoxic action of paracetamol in somatic cells has already been reported for mice bone marrow as chromosomal aberrations (CA) and sister chromatid exchange (SCE) (Giri et al, 1992). Treatment with paracetamol also induced SCE and CA and inhibits replicative DNA synthesis in mouse mammary tumor cell line (Hongslo et al, 1990).…”

Section: Discussionmentioning

confidence: 98%

Effect of Zingiber Officinale on paracetamol-induced genotoxicity in male rats

Salah¹,

Abdouh²,

Booles³

et al. 2012

J. Med. Plants Res.

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The mutagenic effects of paracetamol (acetaminophen) in male rat using in vivo mutagenicity tests, chromosomal aberrations of somatic and germ cells, molecular assay and biochemical were studied. Paracetamol genotoxicity on normal divided cells has been reported. The data obtained showed that the ability of paracetamol to bind and interact with genetic material lead to changes in chromosomal behavior and structure during mitosis. The significant increase in chromosomal aberration, the changes in the number, position and intensity of bands, liver and renal damages induced by paracetamol may be attributed to the fact that paracetamol can induce genotoxicity through DNA damage. Paracetamol also stimulated AST and ALT activity, these stimulations indicated liver cell necrosis. Paracetamol-induced acute renal damage by the elevations in blood urea, uric acid and creatinine levels. Paracetamol showed abnormal values of protein profile in blood. The treatments with ginger presented hepatoprotective effect, also ginger can protect against oxidative kidneys tissue damage that reduced lipid peroxiation in liver and kidneys. The possible mechanism by which ginger exhibited significant protection against paracetamol-induced genotoxicity and hepatotoxicity may be due to its antioxidant effect. It may also be responsible for the hepatoprotective activity and attainment of normal frequencies of chromosomal aberration in ginger-treated rats. Thus, the present study indicated that the genotoxicity products at low concentration and for long time treatment showed the hazard of paracetamol addiction on human's life.

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“…The trend tests for the evidence of doseresponse effects for both sister-chromatid exchange and chromosome aberrations were significant (Giri et al, 1992).…”

Section: Introductionmentioning

confidence: 93%

“…The study of Giri et al (1992) indicates that paracetamol was genotoxic in vivo in bone marrow cells of mice. The trend tests for the evidence of doseresponse effects for both sister-chromatid exchange and chromosome aberrations were significant (Giri et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic Evaluation of Paracetamol Effects in Human Lymphocytes Culture

Ibrulj

Rahmanović

Haverić

et al. 2007

Drug and Chemical Toxicology

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Paracetamol is a common analgesic and antipyretic drug. It has been recognized as one of the most ordinary medications taken in overdoses. We examined the possible genotoxic effects of high paracetamol concentrations expected to occur after overdose. Paracetamol was added to the cultures at the beginning of the cultivation period. Separate cultures for three tested concentrations of paracetamol (50 microg/mL, 100 microg/mL, and 200 microg/mL) were set. Effects of paracetamol were evaluated by micronucleus cytokinesis-block assay, chromosome aberration analysis, and nuclear division index. Results demonstrate that paracetamol concentration of 200 microg/mL expresses certain genotoxic effects in human peripheral blood lymphocytes.

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Sister-chromatid exchange and chromosome aberrations induced by paracetamol in vivo in bone-marrow cells of mice

Cited by 23 publications

References 25 publications

Paracetamol‐Induced Spindle Disturbances in V79 Cells with and without Expression of Human CYP1A2

Paracetamol‐Induced Spindle Disturbances in V79 Cells with and without Expression of Human CYP1A2

Effect of Zingiber Officinale on paracetamol-induced genotoxicity in male rats

Cytogenetic Evaluation of Paracetamol Effects in Human Lymphocytes Culture

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