How cyclophosphamide at environmentally relevant concentration influences Daphnia magna life history and its proteome.

Małgorzata Grzesiuk,Elżbieta Grzesiuk,Damian Mielecki,Damian Garbicz,Tomasz Pilżys,Michał Marcinkowski,Amitava Mukherjee

doi:10.1371/journal.pone.0195366

Małgorzata Grzesiuk, Elżbieta Grzesiuk + Show 5 more

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https://doi.org/10.1371/journal.pone.0195366

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Abstract

The waste of commonly used medicines is known to contaminate freshwater ecosystems. Pharmaceuticals can be toxic, mutagenic, or modifying to freshwater organisms even at low concentrations if consider their permanent presence in the environment. Chemotherapeutics used to treat cancer, and in particular alkylating agents, contribute significantly to this form of pollution, the latter introducing cytotoxic and/or mutagenic lesions to the DNA and RNA of organisms which can be disruptive to their cells. The aim of the present study was to investigate the influence of the alkylating anticancer agent cyclophosphamide (CP) on Daphnia magna clones. We evaluated the life history parameters and protein profiles of this crustacean following exposure to environmentally relevant CP concentration of 10 ng L-1. Even at this low concentration, the alkylating agent caused modification of the life history parameters and proteome profile of the Daphnia. These changes were clone-specific and involved growth rate, age at first reproduction, neonate number, and proteins related to cell cycle and redox state regulation. The disturbance caused by pharmaceuticals contaminating freshwater ecosystem is probably weaker and unlikely to be cytotoxic in character due to the high dilution of these substances in the water. However, our results indicate that prolonged exposure of organisms to these toxins may lead to modifications on the organismal and molecular levels with unpredictable significance for the entire ecosystem.

Highlights

Used pharmaceuticals have been found to be significant pollutants of aquatic ecosystems [1,2,3]
Compared to the untreated controls, the growth rate of the D. magna individuals exposed to CP was lower in all three clones, by approx. 5%, 2.5% and 5% (Fig 2), none of these differences were statistically significant (One way ANOVA clone D: F(1, 17) = 1.81, p = 0.196; clone N: F(1, 17) = 0.386, p = 0.542; clone S: F(1, 15) = 0.671, p = 0.425)
CP had an effect on the age at first reproduction of clone S (Fig 3A), with the individuals maturing later (10 days old) when cultured with CP compared to those Daphnia which were not exposed to the pharmaceutical (9.5 days old) (One way ANOVA: F(1, 18) = 5, p = 0.038)

Summary

Introduction

Used pharmaceuticals have been found to be significant pollutants of aquatic ecosystems [1,2,3] These substances, including anti-cancer agents, have been detected in the surface waters of many countries due to an increase in the consumption of medicines over the past decade [4,5,6]. In 2011, the UK Office of National Statistics predicted that the use of pharmaceuticals in Great Britain would at least double by 2050 (UK Office of National Statistics 2011 https://www.ons.gov.uk). This phenomenon is occurring primarily due to the aging of society as well as the increase in frequency of so-called diseases of affluence, such as type 2. Pharmaceuticals enter sewage treatment plants mainly following their consumption and subsequent excretion by people, or directly by flushing the overdue medicines themselves down toilets [7,8,9]

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