Effects of a synthetic polyprenoic acid (E-5166) on the gap junction of rat hepatocytes treated with liver tumor promoters, phenobarbital, and p,p'-dichlorodiphenyltrichloroethane.
Effects of in vivo exposure to the synthetic polyprenoic acid, 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166) using 6 groups of rats treated simultaneously or individually with phenobarbital (PB) or with p,p'-dichlorodiphenyltrichloroethane (DDT) on the gap junctions of hepatocytes were examined by freeze-fracture analysis. Experimental groups were as follows: Group 1, basal diet alone; Group 2, E-5166 treatment; Group 3, 0.05% PB diet; Group 4, PB diet and E-5166 treatment; Group 5, 0.05% DDT diet; and Group 6, DDT diet and E-5166 treatment. E-5166 was given by gavage (40 mg/kg body weight, 3 times/wk). Experimental diets and E-5166 were started at 6 wk of age. All animals were sacrificed at 2 wk after the start of the experiments. The density of gap junctions in PB- or DDT-treated rats was higher and that in E-5166-treated rats was lower than that in controls. The density of gap junctions in rats given PB and E-5166-/or DDT and E-5166-treated rats was slightly increased when compared to controls. The average area of gap junctions in DDT- or PB and E-5166-treated rats was significantly smaller than in controls (p < 0.005), although no statistical differences were found among PB-, E-5166-, and DDT and E-5166-treated rats and controls. Unit area of gap junctions to membrane area in rats given E-5166, DDT, or PB and E-5166 was lower than in controls. However, the unit area of gap junctions in DDT and E-5166-treated rats did not differ from in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Sugie
S
S
Department of Pathology, Gifu University School of Medicine, Japan.
Tanaka
T
T
Shima
H
H
Shinoda
T
T
Mori
H
H
Muto
Y
Y
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003634:DDT / Q000633:toxicity*; D004347:Drug Interactions; D017629:Gap Junctions / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011912:Rats, Inbred ACI; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology
D002273:Carcinogens; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; D003634:DDT; D010634:Phenobarbital