Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water

Andrea Sapone, Bianca Gustavino, Monica Monfrinotti, Donatella Canistro, Massimiliano Broccoli, Laura Pozzetti, Alessandra Affatato, Luca Valgimigli, Giorgio Cantelli Forti, Gian Franco Pedulli, Gian Luigi Biagi, Sherif Abdel-Rahman, Moreno Paolini

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Epidemiological evidence suggests a link between consumption of chlorinated drinking water and various cancers. Chlorination of water rich in organic chemicals produces carcinogenic organochlorine by-products (OBPs) such as trihalomethanes and haloacetic acids. Since the discovery of the first OBP in the 1970s, there have been several investigations designed to determine the biological effects of single chemicals or small artificial OBP combinations. However, there is still insufficient information regarding the general biological response to these compounds, and further studies are still needed to evaluate their potential genotoxic effects. In the current study, we evaluated the effect of three drinking water disinfectants on the activity of cytochrome P450 (CYP)-linked metabolizing enzymes and on the generation of oxidative stress in the livers of male and female Cyprinus carpio fish (carp). The fish were exposed in situ for up 20 days to surface water obtained from the Trasmene lake in Italy. The water was treated with 1-2 mg/L of either sodium hypochlorite (NaClO) or chlorine dioxide (ClO 2) as traditional disinfectants or with a relatively new disinfectant product, peracetic acid (PAA). Micronucleus (MN) frequencies in circulating erythrocytes from the fish were also analysed as a biomarker of genotoxic effect. In the CYP-linked enzyme assays, a significant induction (up to a 57-fold increase in the deethylation of ethoxyresorufin with PAA treatment) and a notable inactivation (up to almost a 90% loss in hydroxylation of p-nitrophenol with all disinfectants, and of testosterone 2β-hydroxylation with NaClO) was observed in subcellular liver preparations from exposed fish. Using the electron paramagnetic resonance (EPR) spectroscopy radical-probe technique, we also observed that CYP-modulation was associated with the production of reactive oxygen species (ROS). In addition, we found a significant increase in MN frequency in circulating erythrocytes after 10 days of exposure of fish to water treated with ClO 2, while a non-significant six-fold increase in MN frequency was observed with NaClO, but not with PAA. Our data suggest that the use of ClO 2 and NaClO to disinfect drinking water could generate harmful OBP mixtures that are able to perturb CYP-mediated reactions, generate oxidative stress and induce genetic damage. These data may provide a mechanistic explanation for epidemiological studies linking consumption of chlorinated drinking water to increased risk of urinary, gastrointestinal and bladder cancers.

Original languageEnglish (US)
Pages (from-to)143-154
Number of pages12
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume626
Issue number1-2
DOIs
StatePublished - Jan 10 2007

Fingerprint

Carps
Drinking Water
Cytochrome P-450 Enzyme System
Disinfectants
DNA Damage
Peracetic Acid
Fishes
Oxidative Stress
Water
Hydroxylation
Trihalomethanes
Erythrocytes
Organic Chemicals
Sodium Hypochlorite
Gastrointestinal Neoplasms
Halogenation
Liver
Electron Spin Resonance Spectroscopy
Enzyme Assays
Lakes

Keywords

  • Cancer
  • Cyprinus carpio
  • Cytochrome p450
  • Drinking water by-products
  • Micronucleus
  • Organochlorine by-products
  • ROS

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water. / Sapone, Andrea; Gustavino, Bianca; Monfrinotti, Monica; Canistro, Donatella; Broccoli, Massimiliano; Pozzetti, Laura; Affatato, Alessandra; Valgimigli, Luca; Forti, Giorgio Cantelli; Pedulli, Gian Franco; Biagi, Gian Luigi; Abdel-Rahman, Sherif; Paolini, Moreno.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 626, No. 1-2, 10.01.2007, p. 143-154.

Research output: Contribution to journalArticle

Sapone, A, Gustavino, B, Monfrinotti, M, Canistro, D, Broccoli, M, Pozzetti, L, Affatato, A, Valgimigli, L, Forti, GC, Pedulli, GF, Biagi, GL, Abdel-Rahman, S & Paolini, M 2007, 'Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water', Mutation Research - Genetic Toxicology and Environmental Mutagenesis, vol. 626, no. 1-2, pp. 143-154. https://doi.org/10.1016/j.mrgentox.2006.09.010
Sapone, Andrea ; Gustavino, Bianca ; Monfrinotti, Monica ; Canistro, Donatella ; Broccoli, Massimiliano ; Pozzetti, Laura ; Affatato, Alessandra ; Valgimigli, Luca ; Forti, Giorgio Cantelli ; Pedulli, Gian Franco ; Biagi, Gian Luigi ; Abdel-Rahman, Sherif ; Paolini, Moreno. / Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water. In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2007 ; Vol. 626, No. 1-2. pp. 143-154.
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AU - Canistro, Donatella

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AU - Pozzetti, Laura

AU - Affatato, Alessandra

AU - Valgimigli, Luca

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AU - Abdel-Rahman, Sherif

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