Lack of initiation activity of 4-oxo-2-hexenal, a peroxidation product generated from omega-3 polyunsaturated fatty acids, in an in vivo five-week liver assay.
Peroxidation products formed from polyunsaturated lipids have DNA damaging potential. 4-oxo-2-hexenal (4-OHE), generated by the oxidation of omega-3 fatty acids, has been demonstrated to be mutagenic in vitro as assessed in the Ames test. To examine the carcinogenic risk of 4-OHE in vivo, initiation activity was investigated in a five-week liver assay, established to be effective for screening of carcinogenic potential of mutagens. Seven-week-old male F344 rats underwent two-thirds partial hepatectomy (PH) and were administered 4-OHE intragastrically at doses of 128, 80, 64, 40, 32, 20, or 0 mg/kg body weight (b.w.) at 18 hours thereafter, then being fed on diet containing 0.015% 2-acetylaminofluorene from weeks 2 to 4. All rats were given with 0.8 ml/kg b.w. CCl4 at week 3. At week 5, all survivors were sacrificed and initiation activity was assessed with reference to induction of glutathione S-transferase placental form (GST-P) positive foci in the liver. Mortality was significantly increased to 72.7% in the 128 mg/kg b.w. dose group compared with 0.9% in the control group. However, the average number of GST-P positive foci in the "128" dose group was 3.26-/+1.66 foci/cm2, not significantly different from the control value (2.78?1.33). Areas of GST-P positive foci were also similar (1.11-/+0.5 and 1.53-/+1.33 mm2/cm2 in "128" and the control groups, respectively). These results showed 4-OHE to have no significant initiation activity in.
Takasu
Shinji
S
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Tsukamoto
Tetsuya
T
Hirata
Akihiro
A
Kawai
Kazuaki
K
Toyoda
Takeshi
T
Ban
Hisayo
H
Sakai
Hiroki
H
Yanai
Tokuma
T
Masegi
Toshiaki
T
Kasai
Hiroshi
H
Tatematsu
Masae
M
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
C506591:4-oxo-(E)-2-hexenal; D000447:Aldehydes; D015525:Fatty Acids, Omega-3