Toxic effects on model mammalian cells by monohalogenated disinfection byproducts: haloacetic acids and haloacetonitriles

Disinfection processes provide a necessary barrier against waterborne infectious diseases; yet, water disinfectants inadvertently generate environmentally hazardous chemicals called disinfection by-products (DBPs). While a number of individual DBPs have been found to be mutagenic, cytotoxic, genotoxic, carcinogenic, teratogenic and developmentally toxic, the precise mechanisms of toxic action by DBPs is largely unknown. With the recent findings of toxicity pattern associated with halogen and nitrogenous functional groups, haloacetic acids (HAAs) and haloacetonitriles (HANs) were selected as representative carbonaceous and nitrogenous DBPs to make comparisons in terms of genomic DNA damage induction, repair efficiency of induced DNA lesions, and cell cycle alteration using Chinese hamster ovary (CHO) cells as a model mammalian cell system. Both HAAs and HANs are alkylating agents with a halogen atom attached on their carbon atom next to the functional group. The potency of cytotoxicity and genotoxicity induction by monoHAAs and monoHANs is associated with the propensity of the halide to leave the molecule, iodide > bromide > chloride. The microplate-based single cell gel electrophoresis assay was modified to include liquid holding recovery time to measure the reduction of genomic DNA damage level over time. The repair efficiency for monoHAA-induced lesions by CHO cells followed the rank order of iodoacetic acid > chloroacetic acid >> bromoacetic acid. MonoHAN-induced lesions were repaired more efficiently than monoHAA-induced lesions without consistent significant associations among the three monoHANs. Consequently, the contribution of the halogen atom did not correlate well with DNA repair kinetics. HAN treatment followed by the release from the treatment resulted in CHO cells with abnormally high levels of DNA content, which was not observed in HAA-treated cells. It appeared that HANs adversely affected cell cycle progression by interfering with cell division. Altered cell ploidy affects genome instability and is widely associated with cancer progression. HAN-mediated disruption of the cell cycle and the generation of aberrant aneuploid cells may contribute to cancer induction and to adverse pregnancy outcomes associated with consumption of disinfected water observed in epidemiological studies. This is the first study that identifies significant cell cycle alterations by a class of DBPs.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Environ Engr in Civil Engr

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Komaki, Yukako

Contributors dc:contributor

• Mariñas, Benito J.
• Plewa, Michael J.
• Liu, Wen-Tso
• Echigo, Shinya

• Disinfection by-products
• mammalian cell
• genotoxicity
• DNA repair kinetics
• cell cycle alteration

Statement dc:rights

• Copyright 2013 Yukako Komaki

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/46896

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/46896