Tumorigenicity of chloral hydrate, trichloroacetic acid, trichloroethanol, malondialdehyde, 4-hydroxy-2-nonenal, crotonaldehyde, and acrolein in the B6C3F(1) neonatal mouse.
The tumorigenicity of chloral hydrate (CH), trichloroacetic acid (TCA), trichloroethanol (TCE), malondialdehyde (MDA), crotonaldehyde, acrolein, and 4-hydroxy-2-nonenal (HNE) was tested in the B6C3F(1) neonatal mouse. Mice were administered i.p. injections of CH (1000, 2000, 2500, and 5000 nmol per animal), TCA (1000 and 2000 nmol), TCE (1000 and 2000 nmol), MDA (1500 and 3000 nmol), crotonaldehyde (1500 and 3000 nmol), acrolein (75 and 150 nmol), and HNE (750 and 1500 nmol) at 8 and 15 days of age. At 12 months, only male mice treated with the positive control chemicals, 4-aminobiphenyl (500 and 1000 nmol) and benzo[a]pyrene (150 and 300 nmol), had incidences of tumors in the liver significantly higher than the solvent control. Additional male mice were dosed as described above and their livers were excised at 24, 48 h, and 7 days after the final dose. Liver DNA was isolated and analyzed by 32P-postlabeling/high-performance liquid chromatography (HPLC) and HPLC/electrochemical detection for MDA-derived adduct (M(1)G) and 8-oxo-2'-deoxyguanosine (8-OHdG) formation, respectively. At 24 and 48 h after the final dose, CH- and TCA-treated mice exhibited significantly higher M(1)G levels than the controls. 8-OHdG formation was also induced by CH, TCA, and MDA. These results suggest that under these experimental conditions the B6C3F(1) neonatal mouse is not sensitive to carcinogens that induce an increase in endogenous DNA adduct formation through lipid peroxidation or oxidative stress.
Von Tungeln
Linda S
LS
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
Yi
Ping
P
Bucci
Thomas J
TJ
Samokyszyn
Victor M
VM
Chou
Ming W
MW
Kadlubar
Fred F
FF
Fu
Peter P
PP
D000171:Acrolein / Q000633:toxicity; D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002697:Chloral Hydrate / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003433:Crosses, Genetic; D004247:DNA / Q000302:isolation & purification; D018736:DNA Adducts / Q000378:metabolism; D004563:Electrochemistry; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D014238:Trichloroacetic Acid / Q000633:toxicity
D000447:Aldehydes; D002273:Carcinogens; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D002697:Chloral Hydrate; D008315:Malondialdehyde; D014238:Trichloroacetic Acid; D005023:Ethylene Chlorohydrin; D000171:Acrolein; D004247:DNA; C012796:2-butenal; C005849:2,2,2-trichloroethanol; C027576:4-hydroxy-2-nonenal