Potential transmission of the cytogenetic toxic effects of methotrexate in the male germline cells of Swiss mice

Choudhury, Ramesh C.; Ghosh, Subir; Palo, Anil K.

doi:10.1016/s1382-6689(01)00073-4

Cited by 23 publications

(16 citation statements)

References 19 publications

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“…After an interval of 90 min of colchicine treatment, the mice were sacrificed by cerebrospinal dislocation, the testes were dissected out and washed thoroughly in 1% sodium citrate at 37°C to remove the adhered fat, seminiferous tubules were teased out in 0.9% sodium citrate at 37°C and homogenized and slides for spermatogonial metaphase chromosome preparations were made following the flame-drying Giemsa technique detailed earlier (Choudhury et al, 2001). About 50 well-spread spermatogonial metaphases were scanned from each animal.…”

Section: Methodsmentioning

confidence: 99%

“…A modified airdrying technique of Evans et al (1964), detailed in Choudhury et al (2001), was followed for the preparation of slides. From each animal, 50 well-spread primary spermatocytes in metaphase I or in diakinesis stages were scanned.…”

Section: Methodsmentioning

confidence: 99%

“…Sperm smears were prepared out of the sperm collected from the vas deferens following the procedure of Choudhury et al (2001). About 2000 sperm from each animal were examined and the different categories of sperm with abnormal morphology were recorded following the classification of Wyrobek and Bruce (1975).…”

Section: Methodsmentioning

confidence: 99%

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Etoposide‐induced cytogenotoxicity in mouse spermatogonia and its potential transmission

Palo

Sahu

Choudhury

2005

J of Applied Toxicology

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As cancer chemotherapeutic agents are cytogenotoxic but not target-specific during systemic treatment, they affect all the encountered cells including the non-cancerous ones and consequently lead to the recurrence of second malignancy in post-chemotherapeutic cancer survivors. The effects would be persistent if the stem cells were affected. These drugs also may affect germline cells during therapeutic treatments. There is every chance that the effects are transmitted through the germline cells to the gametes and to the next generation if the gonadal mother cells are affected. Such transmission of effects from the post-chemotherapeutic childhood cancer survivors is of serious concern but very little attention has been given so far to such studies. Etoposide (VP-16)--a semi-synthetic epipodophyllotoxin derivative, a DNA non-intercalating agent and a topoisomerase II inhibitor--is prescribed frequently for the treatment of various types of cancers. It is a potent clastogen inducing chromosomal damage both in vitro and in vivo. Its clastogenic effect is indirect through inhibition of the catalytic activity of topoisomerase II enzymes, which maintain the topology of DNA during replication, recombination, transcription, etc. by forming a 'cleavable complex' and facilitate the cleaving and re-ligation of the cleaved DNA to relieve the torsional stress during such events. Transient stabilization of the cleavable complex by etoposide leads to illegitimate ligation of the cleaved DNA. Consequently, single- and double-strand breaks occur. In the present study, the clastogenic potential of three different doses of etoposide (10, 15 and 20 mg kg(-1)) in the male germline of mice was assessed from the dividing spermatogonia after a single exposure for one cell cycle duration at 24 h post-treatment. Transmission of such effects was assessed from the frequency of aberrant primary spermatocytes at week 4 post-treatment and of abnormal sperm at week 8 post-treatment. All three doses of etoposide were found to be clastogenic to the dividing spermatogonia of mice, and mostly chromatid breaks were induced. The effects also were transmitted through the male germline of mice, which was evident from the prevalence of statistically significant increased percentages of aberrant primary spermatocytes at week 4 posttreatment and the higher percentages of abnormal sperm at week 8 post-treatment. Thus, there is every chance that the cytogenotoxic effects of etoposide are transmitted to the next generation through the male germline of post-chemotherapeutic cancer survivors, therefore it is essential to make etoposide target-specific or modulate its effects.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Etoposide‐induced cytogenotoxicity in mouse spermatogonia and its potential transmission

Palo

Sahu

Choudhury

2005

J of Applied Toxicology

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“…Animal studies suggest that 5-FU initially causes a decrease in sperm count and an increase in the number of abnormal sperm. These alterations appear to gradually recover, but it is unclear whether there is a return to baseline since human studies have not been reported [65,66]. NCCN Every 3-6 months for 2 years then every 6 months for year 4 and 5…”

Section: • • Fertilitymentioning

confidence: 99%

Optimizing Adjuvant Therapy and Survivorship Care of Stage III Colon Cancer

Loree

Cheung

2016

Future Oncol.

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The MOSAIC trial demonstrated nearly a decade ago that the addition of oxaliplatin to 5-fluorouracil improves outcomes in the adjuvant treatment of colon cancer, but no new agents have been shown to be superior to standard FOLFOX therapy. Oncologists have refined the use of oxaliplatin containing regimens to optimize outcomes, improved patient selection for multi-agent chemotherapy and expanded survivorship care to meet the needs of the growing number of survivors. In this article, we review the historical contexts of current therapy, appropriate staging investigations, the importance of timely initiation of therapy and key survivorship issues. We also discuss exciting opportunities for change, including reduced duration of adjuvant chemotherapy and the use of circulating tumor cells and DNA in surveillance.

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“…Çünkü kemoterapötik ilaçlar sadece kanser hücrelerini hedeflemezler. Tedavi süresince sağlıklı hücreler de bu ilaçlarla karşılaşırlar (9).…”

Section: Introductionunclassified

Evaluation of genotoxic potential of pemetrexed by using in vitro alkaline comet assay

Çobanoğlu¹,

Çoşkun²,

Çayır³

2017

Marmara Pharmaceutical Journal

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Potential transmission of the cytogenetic toxic effects of methotrexate in the male germline cells of Swiss mice

Cited by 23 publications

References 19 publications

Etoposide‐induced cytogenotoxicity in mouse spermatogonia and its potential transmission

Etoposide‐induced cytogenotoxicity in mouse spermatogonia and its potential transmission

Optimizing Adjuvant Therapy and Survivorship Care of Stage III Colon Cancer

Evaluation of genotoxic potential of pemetrexed by using in vitro alkaline comet assay

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