Toxicities of four anti-neoplastic drugs and their binary mixtures tested on the green alga Pseudokirchneriella subcapitata and the cyanobacterium Synechococcus leopoliensis

Brezovšek, Polona; Eleršek, Tina; Filipič, Metka

doi:10.1016/j.watres.2014.01.007

Cited by 131 publications

(72 citation statements)

References 47 publications

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“…Brezovšek et al [54] observed deviations from the CAand IA-predicted mixture toxicities in binary combinations of antineoplastics (5-fluoruracil, cisplatin, etoposide and imatinib) in algal growth assays using Pseudokirchneriella and Synechococcus. The most pronounced antagonistic interaction resulted in the complete abolishment of the cisplatin-induced algal toxicity by etoposide.…”

Section: Deviations From Concentration Addition And/or Independent Acmentioning

confidence: 99%

Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

Backhaus

2014

Phil. Trans. R. Soc. B

116

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Analytical monitoring surveys routinely confirm that organisms in the environment are exposed to complex multi-component pharmaceutical mixtures. We are hence tasked with the challenge to take this into consideration when investigating the ecotoxicology of pharmaceuticals. This review first provides a brief overview of the fundamental approaches for mixture toxicity assessment, which is then followed by a critical review on the empirical evidence that is currently at hand on the ecotoxicology of pharmaceutical mixtures. It is concluded that, while the classical concepts of concentration addition and independent action (response addition) provide a robust scientific footing, several knowledge gaps remain. This includes, in particular, the need for more and better empirical data on the effects of pharmaceutical mixtures on soil organisms as well as marine flora and fauna, and exploring the quantitative consequences of toxicokinetic, toxicodynamic and ecological interactions. Increased focus should be put on investigating the ecotoxicology of pharmaceutical mixtures in environmentally realistic settings.

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Section: Deviations From Concentration Addition And/or Independent Acmentioning

confidence: 99%

Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

Backhaus

2014

Phil. Trans. R. Soc. B

116

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“…Many of these drugs are designed to act via interactions with DNA function and cell signalling and thus may not affect only cancer cells but also normal dividing cells. Consequently, many of these drugs are genotoxic, mutagenic, carcinogenic, teratogenic, and/or embryotoxic (Kummerer et al 2000;Christensen 1998;Besse et al 2012;Zounkova et al 2010;Brezovsek et al 2014;Parrella et al 2014Parrella et al , 2015 and upon unintentional exposure may be dangerous for humans as well as other organisms.…”

Section: Introductionmentioning

confidence: 99%

Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells

Novak

Žegura

Baebler

et al. 2015

Environ Sci Pollut Res

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In chemotherapy, various anti-cancer drugs with different mechanisms of action are used and may represent different risk of undesirable delayed side effects in treated patients as well as in occupationally exposed populations. The aim of the present study was to evaluate genotoxic potential of four widely used anti-cancer drugs with different mechanisms of action: 5-fluorouracil (5-FU), cisplatin (CDDP) and etoposide (ET) that cause cell death by targeting DNA function and imatinib mesylate (IM) that inhibits targeted protein kinases in cancer cells in an experimental model with human hepatoma HepG2 cells. After 24 h of exposure all four anti-cancer drugs at non-cytotoxic concentrations induced significant increase in formation of DNA double strand breaks (DSBs), with IM being the least effective. The analysis of the changes in the expression of genes involved in the response to DNA damage (CDKN1A, GADD45A, MDM2), apoptosis (BAX, BCL2) and oncogenesis (MYC, JUN) showed that 5-FU, CDDP and ET upregulated the genes involved in DNA damage response, while the anti-apoptotic gene BCL2 and oncogene MYC were downregulated. On the contrary, IM did not change the mRNA level of the studied genes, showing different mechanism of action that probably does not involve direct interaction with DNA processing. Genotoxic effects of the tested anti-cancer drugs were observed at their therapeutic concentrations that may consequently lead to increased risk for development of delayed adverse effects in patients. In addition, considering the genotoxic mechanism of action of 5-FU, CDDP and ET an increased risk can also not be excluded in occupationally exposed populations. The results also indicate that exposure to 5-FU, CDDP and ET represent a higher risk for delayed effects such as cancer, reproductive effects and heritable disease than exposure to IM.

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“…Also, in mixtures, the same toxic effect as induced by single instances of exposure was obtained at much lower concentrations of each single compound, meaning that lower concentrations in mixtures present the same toxicity as a higher single dose (50). Similar effects were observed when testing binary mixtures of selected antineoplastic drugs also on green algae and cyanobacteria indicating that mixtures can have compound-specific and species-specific synergistic or antagonistic effects (68). Authors concluded that single compound toxicity data are not sufficient to predict the aquatic toxicities of such antineoplastic drug mixtures.…”

Section: Antineoplastic Drugs In Cancer Treatmentmentioning

confidence: 56%

Forgotten public health impacts of cancer – an overview

Viegas

Ladeira

Veiga

et al. 2017

Archives of Industrial Hygiene and Toxicology

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Cancer is one of the diseases of greatest concern in developed countries and much effort has been invested in discovering and developing therapeutics for curing cancer. Despite the improvements in antineoplastic therapeutics in the last decades, cancer is still one of the most harmful diseases worldwide. The global burden of cancer also implies financial costs: these can be direct costs, such as those related to treatment, care, and rehabilitation and indirect, which include the loss of economic output due to missed work (morbidity costs) and premature death (mortality costs). There are also hidden costs such as health insurance premiums and nonmedical expenses that are worth noting. This paper intends to present an overview of the generally forgotten impacts that the increasing number of cancer cases can have on the environment, workers who handle antineoplastic drugs, and health services. The knowledge available of each of the impacts will be addressed and discussed regarding the expected development. Overall, lessons learnt reflect on the impact of cancer through aspects not commonly evidenced in the literature or even considered in socio-economic analysis, in part due to the fact that these are difficult to contemplate in direct and indirect cancer costs already defined. Attention may be drawn to the need of continuous investment in prevention to reduce the negative impact on the environment, and in the health of workers who handle antineoplastic drugs for patients' treatment. KEY WORDS: costs of cancer; global burden; occupational healthGlobally, cancer is a growing public health problem. It is the second cause of death (21 %) after cardiovascular diseases (48 %), followed by respiratory diseases (12 %) in the sector of non-communicable diseases or diseases caused by non-infectious and non-transmissible medical conditions (1). Important resources are mobilised in order to improve research on new therapeutics, and ultimately devise a cure for this particular disease. Despite the increase in the effectiveness and specificity of chemotherapeutic treatments, cancer still remains one of the most harmful diseases (2-4).In 2012, worldwide incidence of cancer rose to an estimated 14 million new cases per year, with an estimated 8.2 million cancer deaths. The most common cancers diagnosed were of lung (1.8 million cases, 13 %), breast (1.7 million, 11.9 %) and colon (1.4 million, 9.7 %) (1

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Toxicities of four anti-neoplastic drugs and their binary mixtures tested on the green alga Pseudokirchneriella subcapitata and the cyanobacterium Synechococcus leopoliensis

Cited by 131 publications

References 47 publications

Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells

Forgotten public health impacts of cancer – an overview

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