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ANALYSIS OF DNA STRAND BREAKS INDUCED IN RODENT LIVER IN VIVO, HEPATOCYTES IN VITRO, AND A HUMAN CELL LINE BY CHLORINATED ACETIC ACIDS AND ALDEHYDES
Citation:
Chang, L., F. Daniel, AND A.B. DeAngelo. ANALYSIS OF DNA STRAND BREAKS INDUCED IN RODENT LIVER IN VIVO, HEPATOCYTES IN VITRO, AND A HUMAN CELL LINE BY CHLORINATED ACETIC ACIDS AND ALDEHYDES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/108 (NTIS PB93180974), 1992.
Description:
An alkaline unwinding assay was used to quantitate DNA strand breaks (DNA SB) in the livers of rats and mice, in rodent hepatocytes, and in CCRF-CEM cells following treatment with tri- (TCA), di- (DCA) and mono-(MCA) chloroacetic acid and tri-(CH), di)(DCAA) and mono- (CAA) chloroacetaldehyde. one of the acids induced DNA SB in rats but TCA and DCA did produce a small amount of SB in mice (7% at 4 hours) but not at one hour. ontinuous exposure of mice to DCA in the drinking water did not induce hepatic DNA DB although peroxisome proliferation, as evidenced by an increased cyanide-insensitive palmitoyl CoA oxidase activity (PCOA), was stimulated to 490% (7 days) and 652% (14 days) of control. ENA (0.1 g.L) produced DNA damage after 7 days (73% of control) and 14 days (57% of control). ong term exposure of rats (30 weeks) to 2 g/L DCA in the drinking water, a level which increased PCOA to 364% of the control value, gave no DNA damage. he chloroacetalydehydes did not induce DNA SB in cultured rat and mouse hepatocytes at concentrations below those which yielded cytotoxicity. he chloroacetic acids were also ineffective in the CCRF-CEM cells. CAA and CAA, did induce DNA SB in the CCRF-CEM cells at concentrations below those which yielded cytotoxicity. rior incubation of these two chemicals with a rat S9 liver homogenate eliminated the DNA damaging activity. he chloroacetic acids also failed to induce DNA strand breaks in splenocytes and epithelial cells derived from the stomach and duodenum of mice treated in vivo.