Sister chromatid exchanges in adult epileptic patients on phenytoin therapy

Schaumann, Blanka A.; Johnson, Sue Barden; Wang, Nancy; Brunt, Suzanne van

doi:10.1002/em.2860070509

Cited by 18 publications

(13 citation statements)

References 11 publications

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“…Kulkarni et al (1984) and Schaumann et al (1985) reported similar increases in SCE of 6 and 12 adult patients with epilepsy receiving PHT monotherapy, respectively. No difference between adult, PHT-treated patients and controls was observed by Sinues et al, however (1982).…”

supporting

confidence: 57%

“…Among the in vivo studies of PHT-treated children with epilepsy, Hunke and Carpenter (1978) reported negative findings in 10 patients, and Habedank et al (1982) observed increased SCE frequencies in 9 patients as compared with healthy children. Kulkarni et al (1984) and Schaumann et al (1985) reported similar increases in SCE of 6 and 12 adult patients with epilepsy receiving PHT monotherapy, respectively. No difference between adult, PHT-treated patients and controls was observed by Sinues et al, however (1982).…”

mentioning

confidence: 73%

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Lack of Sister Chromatid Exchange Induction in Phenytoin‐Treated Patients with Epilepsy

Schaumann¹,

Winge²,

Garry

1989

Epilepsia

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Phenytoin (PHT) has been suspected of having a mutagenic effect with chronic administration, but the existing evidence is equivocal. Contradictory results have been obtained using different testing systems. Sister chromatid exchange (SCE), a sensitive indicator of genotoxic environmental influences, has been used in only a few limited studies of PHT users, with varying results. The present study was designed to evaluate the potential mutagenicity of PHT in a more objective and reliable way than has been done previously. Following careful screening procedures, 16 adult male patients with epilepsy receiving long-term PHT monotherapy and 16 healthy controls were selected for a study of SCE frequencies in peripheral lymphocytes. The patients and controls were matched for sex, age, and smoking habits. Strict exclusionary criteria were observed, including all factors known to affect or suspected of affecting the SCE frequencies. Statistical analyses did not reveal any significant differences between the SCE rates of PHT-treated patients and controls, indicating a lack of PHT mutagenicity as expressed by induction of SCE in adults.

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supporting

confidence: 57%

mentioning

confidence: 73%

Lack of Sister Chromatid Exchange Induction in Phenytoin‐Treated Patients with Epilepsy

Schaumann¹,

Winge²,

Garry

1989

Epilepsia

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“…Guron et al (1985) and Schaumann et al (1985a) reported lack of SCE induction by CBZ. Concerning the in vivo studies of AED-treated epileptic individuals, Hunke and Carpenter (1978) failed to find a significant difference between SCE rates in epileptics treated with PHT and controls, whereas Habedank et al (1982) and Schaumann et al (1985b) observed increased SCE rates in child and adult patients with PHT monotherapy, respectively. Kulkarni et al (1984) reported a significant increase in SCE of epileptic patients treated PHT and/or PB as compared with controls.…”

Section: Resultsmentioning

confidence: 95%

Effects of antiepileptic drugs and organic brain damage on SCE frequency in cerebral palsies.

Yamamoto¹,

Kohnosu²,

Nakagawara

et al. 1990

Tohoku J. Exp. Med.

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In order to assess the genotoxic effects of antiepileptic drugs (AEDs), analysis of sister chromatid exchanges (SCEs) was performed in lymphocytes of three groups of males ; epileptics with AED therapy, non-epileptics without AED therapy and healthy controls. The epileptics and non-epileptics were cases of severe cerebral palsies due to perinatal asphyxia. Possible confounding factors of SCE frequencies, such as age, smoking habit, drug usage other than AED, recent history of viral infection, etc. were controlled. The frequency of SCE per cell was 4.63+0.71 (mean±s.n.) in epileptics, 4.70+0.89 in non-epileptics and 3.84+0.56 in healthy controls. SCEs in both epileptics and non-epileptics were significantly higher (p <0.05) than those in controls. There was no significant difference of SCE frequency between epileptics and non-epileptics. These results suggested that no mutagenic effect of AED could be demonstrated as revealed by SCEs, and organic brain damage per se might influence the baseline SCE frequency. The possible explanations for such observations are discussed.sister chromatid exchange (SCE); antiepileptic drug ; cerebral palsy ; brain damage Patients with severe organic brain damage are frequently complicated by intractable epilepsy, and long term therapy with two or more antiepileptic drugs (AEDs) is usually necessary. Therefore, these patients may be particularly subject to various adverse effects of AEDs. Among them, genotoxicity of AEDs presents one of the most important medical problems.Sister chromatid exchange (SCE) involves a symmetrical exchange between two chromatids of one chromosome. Since the original report of Perry and Evans (1975), SCE has been recognized as a sensitive indicator of DNA damage and repair and widely used not only as a useful in vitro test to assess the mutagenic

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“…On the other hand, in vivo studies of cell cycle analysis by Schaumann et al [11] did not reveal any significant difference between CBZ-treated patients and controls.…”

Section: Discussionmentioning

confidence: 95%

“…In vivo studies by Schaumann et al [11] showed no significant difference in cell cycle analysis between CBZ-treated patients and controls. The report by Goyle et al [12,13] provided a general assessment of mutagenicity in epileptic patients and emphasised the role of the disease in the higher occurrence of congenital malformations in their offspring.…”

Section: Introductionmentioning

confidence: 97%

Genotoxicity of the anticonvulsant drug phenytoin (PHT): A follow-up study of PHT-untreated epileptic patients. II. Mitotic index (MI) and proliferation kinetics

Kaul

Goyle

1999

Teratog. Carcinog. Mutagen.

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The mitotic index and proliferation rate index were investigated to determine the effect of phenytoin (PHT) in cultured blood lymphocytes of epileptics prior to and following administration of PHT over a period of 9 months (grouped in multiples of 3 months) and 40 control subjects (age range 10–30 years). Treatment with PHT brought inhibition of the mitotic index (MI) and proliferation rate index (PRI), which were significantly higher in treated subjects or which were more expressive in treated lymphocytes (P < 0.001) for all the three durations of treatment. In addition, statistically significant heterogeneity of first, second, and third metaphases between the treated, untreated, and control subjects was found. Mean PRI values were used to estimate cell cycle delays, showing the highest effect in treated lymphocytes (P < 0.001). There was no considerable variation between the control and untreated (P > 0.05). The study demonstrates that PHT may be potentially genotoxic and hence the usefulness of MI and PRI in monitoring epileptics on anticonvulsant treatment. Teratogenesis Carcinog. Mutagen. 19:73–84, 1999. © 1999 Wiley‐Liss, Inc.

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Sister chromatid exchanges in adult epileptic patients on phenytoin therapy

Cited by 18 publications

References 11 publications

Lack of Sister Chromatid Exchange Induction in Phenytoin‐Treated Patients with Epilepsy

Lack of Sister Chromatid Exchange Induction in Phenytoin‐Treated Patients with Epilepsy

Effects of antiepileptic drugs and organic brain damage on SCE frequency in cerebral palsies.

Genotoxicity of the anticonvulsant drug phenytoin (PHT): A follow-up study of PHT-untreated epileptic patients. II. Mitotic index (MI) and proliferation kinetics

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