Multiple genotoxic activities of ptaquiloside in human lymphocytes: Aneugenesis, clastogenesis and induction of sister chromatid exchange

Costa, Rui M. Gil da; Coelho, Patrícia; Sousa, Rosa; Bastos, Margarida; Porto, Beatriz; Teixeira, João Paulo; Malheiro, Isabel; Lopes, Carlos

doi:10.1016/j.mrgentox.2012.04.010

Cited by 17 publications

(10 citation statements)

References 28 publications

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Section: Bracken Fern and Bpv In Upper Digestive Carcinogenesismentioning

confidence: 85%

“…The first involves their genotoxic effects, as these compounds are able to alkylate DNA and induce point mutations, namely activating mutations at the Harvey rat sarcoma (H-ras) proto-oncogene codons 58, 58 and 61 ( 102 , 103 ), which lead to increased cell proliferation. Ptaquiloside also induces chromosome aberrations ( 104 , 105 ) that ultimately lead to a neoplastic phenotype, as previously reviewed ( 24 ). The second way involves their immune suppressive properties, which may facilitate the persistence of oncogenic viruses like BPV and HPV and may also allow early neoplastic lesions to evade immunological surveillance and develop into overt cancers ( 27 ).…”

Section: Bracken Fern and Bpv In Upper Digestive Carcinogenesismentioning

confidence: 87%

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Pteridium spp. and Bovine Papillomavirus: Partners in Cancer

et al. 2021

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Bovine papillomavirus (BPV) are a cause for global concern due to their wide distribution and the wide range of benign and malignant diseases they are able to induce. Those lesions include cutaneous and upper digestive papillomas, multiple histological types of urinary bladder cancers—most often associated with BPV1 and BPV2—and squamous cell carcinomas of the upper digestive system, associated with BPV4. Clinical, epidemiological and experimental evidence shows that exposure to bracken fern (Pteridium spp.) and other related ferns plays an important role in allowing viral persistence and promoting the malignant transformation of early viral lesions. This carcinogenic potential has been attributed to bracken illudane glycoside compounds with immune suppressive and mutagenic properties, such as ptaquiloside. This review addresses the role of BPV in tumorigenesis and its interactions with bracken illudane glycosides. Current data indicates that inactivation of cytotoxic T lymphocytes and natural killer cells by bracken fern illudanes plays a significant role in allowing viral persistence and lesion progression, while BPV drives unchecked cell proliferation and allows the accumulation of genetic damage caused by chemical mutagens. Despite limited progress in controlling bracken infestation in pasturelands, bracken toxins remain a threat to animal health. The number of recognized BPV types has steadily increased over the years and now reaches 24 genotypes with different pathogenic properties. It remains essential to widen the available knowledge concerning BPV and its synergistic interactions with bracken chemical carcinogens, in order to achieve satisfactory control of the livestock losses they induce worldwide.

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Section: Bracken Fern and Bpv In Upper Digestive Carcinogenesismentioning

confidence: 85%

Section: Bracken Fern and Bpv In Upper Digestive Carcinogenesismentioning

confidence: 87%

Pteridium spp. and Bovine Papillomavirus: Partners in Cancer

et al. 2021

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“…Previous studies have shown chromosomal aberrations in the lymphocytes of cows and humans who had consumed bracken fern (Lioi et al, 2004;Recouso et al, 2003), as well as in lymphocytes that had been treated in vitro with ptaquiloside (Gil da Costa et al, 2012b). This genotoxic effect might be responsible for the increased expression of genes associated with DNA damage repair and the negative regulation of apoptosis, such as Tsc22d3, Sycp3 and Xrcc2, observed in the splenic NK cells of mice treated with ptaquiloside (Table 2).…”

Section: Discussionmentioning

confidence: 94%

Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium

et al. 2013

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Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans. Moreover, our previous studies showed that the immunosuppressive effects of ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cells. We also verified that this immunosuppression facilitated development of cancer. Here, we performed gene expression microarray analysis in splenic NK cells from mice treated for 14 days with ptaquiloside (5.3 mg/kg) and/or selenium (1.3 mg/kg) to identify gene transcripts altered by ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium. Transcriptome analysis of ptaquiloside samples revealed that 872 transcripts were expressed differentially (fold change>2 and p<0.05), including 77 up-regulated and 795 down-regulated transcripts. Gene ontology analysis mapped these up-regulated transcripts to three main biological processes (cellular ion homeostasis, negative regulation of apoptosis and regulation of transcription). Considering the immunosuppressive effect of ptaquiloside, we hypothesized that two genes involved in cellular ion homeostasis, metallothionein 1 (Mt1) and metallothionein 2 (Mt2), could be implicated because Mt1 and Mt2 are responsible for zinc homeostasis, and a reduction of free intracellular zinc impairs NK functions. We confirm these hypotheses and show increased expression of metallothionein in splenic NK cells and reduction in free intracellular zinc following treatment with ptaquiloside that were completely prevented by selenium co-treatment. These findings could help avoid the higher susceptibility to cancer that is induced by P. aquilinum-mediated immunosuppressive effects.

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“…Mitomycin C (400 ng mL -1 ) was used as a positive control. Pirimor-50 ® was dissolved in 1 % DMSO, concentration that did not affect the SCE frequency according to our previous results (not shown here) and to the results of other studies (30)(31)(32). Preliminary experiments were performed in order to identify the optimal concentrations of Pirimor-50 ® that did not cause cell death.…”

Section: Treatment Of Human Lymphocyte Culturesmentioning

confidence: 94%

Genotoxic effects of the carbamate insecticide Pirimor-50® in Vicia faba root tip meristems and human lymphocyte culture after direct application and treatment with its metabolic extracts

Valencia-Quintana

Gómez‐Arroyo

Sánchez-Alarcón

et al. 2016

Archives of Industrial Hygiene and Toxicology

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The aim of the study was to evaluate genotoxic effects of Pirimor-50 ® , a pirimicarb-based formulation (50 % active ingredient), in human lymphocyte cultures and Vicia faba root meristems. Furthermore, the objective was to examine a combined influence of insecticide treatment with mammalian microsomal S9 and vegetal S10 metabolic fractions or S10 mix metabolic transformation extracts (after Vicia faba primary roots treatment with Pirimor-50 ® ). We used sister chromatid exchange assay-SCE and measured cell cycle progression and proliferation (proportion of M 1 -M 3 metaphases and replication index ratio-RI). Two processes were used for plant promutagen activation: in vivo activation-Pirimor-50 ® was applied for 4 h to the plant and then S10 mix was added to lymphocytes; and, in vitro activation-lymphocytes were treated with Pirimor-50 ® and S10 or S9 for 2 h. Direct treatment induced significantly higher SCE frequencies in meristems at 0.01 mg mL -1 . In lymphocytes, significantly higher SCE was at 1 mg mL -1 with decrease in RI and M 1 -M 3 metaphase proportions at 0.5 mg mL -1 and cell division stop at 2.5 mg mL 1 . S10 mix lymphocyte treatment showed significantly elevated SCE values at 2-2.5 mg mL -1 , with cell death at 3 mg mL -1. Lymphocyte treatment with Pirimor-50 ® together with S9 or S10 showed slightly elevated SCE frequency but had a significant influence on RI decrease, with lowest values in S9 treatment. Since no data are available on the genotoxicity of Pirimor-50 ® , this study is one of the first to evaluate and compare its direct effect in two bioassays, animal and vegetal, and also the effect of plant and animal metabolism on its genotoxic potential.

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Multiple genotoxic activities of ptaquiloside in human lymphocytes: Aneugenesis, clastogenesis and induction of sister chromatid exchange

Cited by 17 publications

References 28 publications

Pteridium spp. and Bovine Papillomavirus: Partners in Cancer

Pteridium spp. and Bovine Papillomavirus: Partners in Cancer

Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium

Genotoxic effects of the carbamate insecticide Pirimor-50® in Vicia faba root tip meristems and human lymphocyte culture after direct application and treatment with its metabolic extracts

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