Chromosome aberration frequency in rat peripheral lymphocytes increases with repeated dosing with hexamethylphosphoramide or cyclophosphamide

Doherty, Ann; Hayes, J. F.; Holme, Paul; O’Donovan, Mike

doi:10.1093/mutage/ges016

Cited by 8 publications

(6 citation statements)

References 17 publications

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“…The literature surrounding HMPA is considerably sparser relative to the other progenotoxicants studied herein. Reports by Sarrif et al [] and Doherty et al [], suggest that formaldehyde is the proximate genotoxicant. However, the known appreciable cytotoxicity of formaldehyde, and the lack of cytotoxicity observed in our experiments, supports our premise that HMPA was not effectively bioactivated by the S9 reagent that we used, thus the lack of γH2AX and p53 responses was not surprising.…”

Section: Resultsmentioning

confidence: 99%

γH2AX and p53 responses in TK6 cells discriminate promutagens and nongenotoxicants in the presence of rat liver S9

Bernacki

Bryce

Bemis

et al. 2016

Environ and Mol Mutagen

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Previous work with a diverse set of reference chemicals suggests that an in vitro multiplexed flow cytometry-based assay (MultiFlow™ DNA Damage Kit—p53, γH2AX, Phospho-Histone H3) can distinguish direct-acting clastogens and aneugens from non-genotoxicants [Environ Mol Mutagen 57(2016)171-189]. The current work extends this line of investigation to include compounds that require metabolic activation to form reactive electrophiles. For these experiments TK6 cells were exposed to 11 promutagens and 37 presumed non-genotoxicants in 96 well plates. Unless precipitation or foreknowledge about cytotoxicity suggested otherwise, the highest concentration was 1 mM. Exposure occurred for 4 hrs after which time cells were washed to remove S9 and test article. Immediately following the wash and again at 24 hrs, cell aliquots were added to wells of a microtiter plate containing the working detergent/stain/antibody cocktail. After a brief incubation robotic sampling was employed for walk-away flow cytometric data acquisition. Univariate logistic regression analyses indicated that γH2AX induction and p53 activation provide the greatest degree of discrimination between clastogens and non-genotoxicants. Multivariate prediction algorithms that incorporated both of these endpoints, in each combination of time points, were evaluated. The best performing models correctly predicted 9 clastogens out of 11 and 36 non-genotoxicants out of 37. These results are encouraging as they suggest that an efficient and highly scalable multiplexed assay can effectively identify clastogenic chemicals that require bioactivation. More work is planned with a broader range of chemicals, additional cell lines, and other laboratories in order to further evaluate the merits and limitations of this approach.

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Section: Resultsmentioning

confidence: 99%

γH2AX and p53 responses in TK6 cells discriminate promutagens and nongenotoxicants in the presence of rat liver S9

Bernacki

Bryce

Bemis

et al. 2016

Environ and Mol Mutagen

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“…Cyclophosphamide's chemically reactive metabolic products induce cytotoxicity by alkylating DNA and proteins (3). Cyclophosphamide is known as human carcinogen and has an increased incidence of chromosome aberrations in lymphocytes from patients with malignant and non-malignant diseases (6). The genotoxicity of cyclophosphamide has been studied in a variety of in vivo and in vitro systems, mutagenic, teratogenic and carcinogenic, and is routinely used as a positive control in genotoxicity tests (1,6).…”

Section: U N C O R R E C T E D P R O O F Introductionmentioning

confidence: 99%

“…Cyclophosphamide is known as human carcinogen and has an increased incidence of chromosome aberrations in lymphocytes from patients with malignant and non-malignant diseases (6). The genotoxicity of cyclophosphamide has been studied in a variety of in vivo and in vitro systems, mutagenic, teratogenic and carcinogenic, and is routinely used as a positive control in genotoxicity tests (1,6). Natural compounds find application in the treatment of refractory diseases, a new trend in modern clinical medicine (7).…”

Section: U N C O R R E C T E D P R O O F Introductionmentioning

confidence: 99%

Assessment of in vitro antigenotoxic effect of nigella sativa oil

Zor¹,

Kurtoğlu²

2020

tjps

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INTRODUCTION: Cyclophosphamide is an alkylating agent widely used as an antineoplastic and immunosuppressive agent. The genotoxicity of cyclophosphamide has been studied in a variety of in vivo and in vitro systems and is routinely used as a positive control in genotoxicity tests. Traditional medicine Nigella sativa L., (Nigella), Ranunculaceae family, especially in the Eastern Mediterranean countries, especially in many countries, and is widely used in many countries as a spice and folk medicine since the time of Dioscorides used as a plant. In this study, it was aimed to show the protective effects of Nigella sativa oil at different concentrations against the genotoxic effects of Cyclophosphamide by micronucleus test. METHODS: For this purpose, healthy cells were treated in vitro with Nigella sativa oil at concentrations of 1, 5, 10 µg / mL and Cyclophosphamide as positive control for 68 hours. The micronuclei were then counted. RESULTS: No significant increase in micronucleus frequency was observed when the application of Nigella Sativa oil at concentrations of 1, 5, 10 µg / mL compared with the negative control. There was a decrease in the number of micronucleus in all three concentrations (1, 5, 10 µg / mL) compared to the Cyclophosphamide group in the groups treated with Nigella sativa oil and cyclophosphamide. DISCUSSION AND CONCLUSION: It has been shown that nigella sativa oil may have protective effects against genotoxicity agents in vitro. But more work is needed to understand the mechanism of the genotoxicity effects of nigella sativa oil.

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“…3 CP is known as human carcinogen and has an increased incidence of chromosome aberrations in lymphocytes from patients with malignant and non-malignant diseases. 6 The genotoxicity of CP has been studied in a variety of in vivo and in vitro systems, mutagenic, teratogenic and carcinogenic, and is routinely used as a positive control in genotoxicity tests. 1,6 Natural compounds find application in the treatment of refractory diseases, a new trend in modern clinical medicine.…”

Section: Introductionmentioning

confidence: 99%

“…6 The genotoxicity of CP has been studied in a variety of in vivo and in vitro systems, mutagenic, teratogenic and carcinogenic, and is routinely used as a positive control in genotoxicity tests. 1,6 Natural compounds find application in the treatment of refractory diseases, a new trend in modern clinical medicine. 7 Nigella sativa (N. sativa) is a short-lived annual plant of the Ranunculaceae family, known as black seed, black cumin and fennel flower.…”

Section: Introductionmentioning

confidence: 99%

Assessment of <i>In Vitro</i> Antigenotoxic Effect of <i>Nigella Sativa</i> Oil

Zor¹,

Kurtoğlu²

2020

tjps

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ÖZAmaç: Siklofosfamid, antineoplastik ve immünosüpresif ajan olarak yaygın olarak kullanılan alkilleyici bir ajandır. Siklofosfamid'in genotoksisitesi çeşitli in vivo ve in vitro sistemde çalışılmış ve rutin olarak genotoksisite testlerinde pozitif kontrol olarak kullanılmaktadır. Geleneksel tıp da Nigella sativa L. (N. sativa), Ranunculaceae familyasından olup günümüzde başta Doğu Akdeniz ülkeleri olmak üzere birçok ülkede yaygın olarak yetişen ve hem baharat hem de halk ilacı olarak Dioscorides zamanından beri kullanılan bir bitkidir. Bu çalışmada Siklofosfamid'in genotoksik etkilerine karşı çörek otu yağının değişik konsantrasyonlardaki koruyucu etkilerininin mikronükleus testi ile gösterilmesi amaçlanmıştır. Gereç ve Yöntemler: Bu amaçla, sağlıklı hücreler 1, 5, 10 µg/mL konsantrasyonlarında N. sativa yağı ile ve pozitif kontrol olarak Siklofosfamid ile 68 saat boyunca in vitro muamele edildi. Daha sonra ise mikronükleuslar sayıldı. Bulgular: N. sativa yağının 1, 5, 10 µg/mL konsantrasyonlarındaki uygulaması negatif kontrolle karşılaştırıldığında mikronükleus frekansında anlamlı bir artış gözlenmedi. N. sativa yağı ve Siklofosfamid'in birlikte uygulandığı gruplarda her üç konsantrasyonda da (1, 5, 10 µg/mL) Siklofosfamid grubuna göre mikronükleus sayısında azalma olduğu görüldü. Sonuç: N. sativa yağının genotoksisite ajanlarına karşı in vitro koruyucu etkilerinin olabileceği gösterilmiştir. N. sativa yağının genotoksisiteyi giderici etkilerinin mekanizmasının anlaşılması için daha fazla çalışmaya ihtiyaç vardır. ABSTRACTObjectives: Cyclophosphamide (CP) is an alkylating agent widely used as an antineoplastic and immunosuppressive agent. The genotoxicity of CP has been studied in a variety of in vivo and in vitro systems and is routinely used as a positive control in genotoxicity tests. Traditional medicine Nigella sativa L., (N. sativa), Ranunculaceae family, especially in the Eastern Mediterranean countries, especially in many countries, and is widely used in many countries as a spice and folk medicine since the time of Dioscorides used as a plant. In this study, it was aimed to show the protective effects of N. sativa oil at different concentrations against the genotoxic effects of CP by micronucleus test. Materials and Methods: For this purpose, healthy cells were treated in vitro with N. sativa oil at concentrations of 1, 5, 10 µg/mL and CP as positive control for 68 hours. The micronuclei were then counted. Results: No significant increase in micronucleus frequency was observed when the application of N. sativa oil at concentrations of 1, 5, 10 µg/mL compared with the negative control. There was a decrease in the number of micronucleus in all three concentrations (1, 5, 10 µg/mL) compared to the CP group in the groups treated with N. sativa oil and CP. Conclusion: It has been shown that N. sativa oil may have protective effects against genotoxicity agents in vitro. But more work is needed to understand the mechanism of the genotoxicity effects of N. sativa oil.

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Chromosome aberration frequency in rat peripheral lymphocytes increases with repeated dosing with hexamethylphosphoramide or cyclophosphamide

Cited by 8 publications

References 17 publications

γH2AX and p53 responses in TK6 cells discriminate promutagens and nongenotoxicants in the presence of rat liver S9

γH2AX and p53 responses in TK6 cells discriminate promutagens and nongenotoxicants in the presence of rat liver S9

Assessment of in vitro antigenotoxic effect of nigella sativa oil

Assessment of <i>In Vitro</i> Antigenotoxic Effect of <i>Nigella Sativa</i> Oil

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