Cytotoxic and mutagenic effects of ferric nitrilotriacetate on L5178Y mouse lymphoma cells.
An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular necrosis that leads to a high incidence of renal adenocarcinoma in rodents. Others have shown that Fe-NTA induces modified DNA base products both in vitro and in vivo. However, Fe-NTA is negative in the Ames Salmonella test with or without S9 activation. The goal of this project was to determine if Fe-NTA is cytotoxic and mutagenic using the L5178Y (TK +/-) mouse lymphoma assay. Our experiments showed a relationship between the concentration of Fe-NTA (0 to 1 mM) and the decrease in relative survival. An exposure-dependent increase in the number of mutations was observed with increasing concentrations of Fe-NTA. At 14% relative survival, there was about a 4-fold increase in mutations (trifluorothymidine resistance) over unexposed, control cells. Ferric nitrate or nitrilotriacetic acid alone induced a relatively low 1.5- or 1.1-fold increase in mutation, respectively. Our results establish that Fe-NTA is mutagenic in the L5178Y mouse lymphoma assay system.
Toyokuni
S
S
U.S. Food and Drug Administration, Rockville, MD 20857.
Sagripanti
J L
JL
Hitchins
V M
VM
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D005290:Ferric Compounds / Q000633:toxicity*; D007700:Kinetics; D007940:Leukemia L5178 / Q000188:drug therapy*; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002273:Carcinogens; D005290:Ferric Compounds; D009153:Mutagens; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate