Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice.
2,4-Hexadienal (2,4-Hx) was studied for its toxicity and carcinogenicity because of its alpha, beta-unsaturated aldehyde structure and potential link between exposure to lipid peroxidation products in the diet and human malignancies. Male and female F344N rats and B6C3F1 mice received 2,4-Hx in corn oil by gavage for 16 days, 14 weeks, or 2 years. In the 16-day studies 2,4-Hx induced forestomach necrosis and ulceration at 240 mg/kg and forestomach epithelial hyperplasia at 80 mg/kg in rats and mice. In the 14-week studies the chemical induced forestomach hyperplasia and nasal olfactory atrophy or necrosis at 120 mg/kg in rats and mice. In the 2-year studies 2,4-Hx induced squamous cell papilloma and carcinoma of the forestomach in male and female rats at 45 and 90 mg/kg and in male and female mice at 120 mg/kg. Two male mice in the 120 mg/kg group had uncommon squamous cell carcinoma of the oral cavity (tongue). Mechanistic studies indicated that the forestomach carcinogenesis in rats and mice may be due to depletion of glutathione as a result of oxidative stress induced by 2,4-Hx.
Chan
Po C
PC
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. chanp@niehs.nih.gov
Mahler
Joel
J
Peddada
Shyamal
S
Lomnitski
Liat
L
Nyska
Abraham
A
D000284:Administration, Oral; D000447:Aldehydes / Q000633:toxicity*; D000466:Alkadienes / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D005503:Food Additives / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006965:Hyperplasia; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018307:Neoplasms, Squamous Cell / Q000139:chemically induced / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology
D000447:Aldehydes; D000466:Alkadienes; D002273:Carcinogens; D005503:Food Additives; C079389:2,4-hexadienal; D005978:Glutathione