Anti-cancer drugs in aquatic environment can cause cancer: Insight about mutagenicity in tadpoles

Abstract

Cyclophosphamide (Cyc) and 5-fluorouracil (5-FU) are two of the most used antineoplastic drugs (AD) in the world. However, their discharge in the environment became a yet-unknown environmental issue that has impact on some groups of animals, such as amphibians. We assessed tadpoles (Lithobates catesbeianus) exposed to environmental concentrations (EC) of Cyc and 5-FU to evaluate whether they can cause morphological and mutagenic changes in them. We defined the following groups: control, positive control (50 mg/L of Cyc), EC-Cyc-I (0.2 μg/L), EC-Cyc-II (0.5 μg/L), EF-Cyc (2.0 μg/L), EC-5-FU-I (13.0 μg/L), EC-5-FU-II (30.4 μg/L) and EF-5-FU (123.5 μg/L). EC groups presented predictive AD concentrations in 10% and 25% hospital-effluent dilutions in water. EF groups met gross hospital-effluent concentrations. Based on our data, ADs caused intestinal changes and influenced the interocular distance in tadpoles after 30-day exposure. We also observed the aneugenic and clastogenic effect of ADs due to the higher frequency of micronucleated and binucleated erythrocytes, and blebbed, multilobulated, notched and kidney-shaped nuclei in animals exposed to them. Based on such changes, we assume that Cyc and 5-FU can trigger malignant cell transformation processes, and cancer, in animals exposed to them, even at low concentrations. Our study is the first to describe that Cyc and 5-FU, spread in the environment, cause damages in non-target organisms opposite to their original end.