Toxicity, DNA binding, and cell proliferation in male F344 rats following short-term gavage exposures to trans-2-hexenal.
Hexenal is a genotoxic compound to which humans are exposed daily through the consumption of foods and beverages. The present studies were conducted to examine the relationships between the dose-responses of trans-2-hexenal-induced toxicity, DNA adduct formation, and cell proliferation. Male F344 rats were exposed by gavage to single doses of up to 500 mg/kg and killed 1, 2, or 4 days after dosing or were exposed to repeat doses of up to 100 mg/kg once daily for 5 days or 5 days per week for 4 weeks and killed 1 day after the end of the dosing period. Histologically, the primary observations were necroulcerative lesions, inflammation, and hyperplasia in the forestomach and inflammation in the glandular stomach. Hexenal-derived DNA adduct formation and cell proliferation were induced in the forestomach at doses of hexenal that also induced gastric toxicity; DNA adducts were not observed in the glandular stomach. These findings suggest that the toxicity of hexenal was limited to the site of contact (stomach) and that the observed DNA adduct formation and cell proliferation occurred in the setting of severe tissue damage.
Stout
Matthew D
MD
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA.
Bodes
Elmarie
E
Schoonhoven
Robert
R
Upton
Patricia B
PB
Travlos
Gregory S
GS
Swenberg
James A
JA
D000284:Administration, Oral; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019963:Clinical Chemistry Tests; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006403:Hematologic Tests; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests
D000447:Aldehydes; D018736:DNA Adducts; D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen; C051750:2-hexenal; D004247:DNA; D003849:Deoxyguanosine