The effect of butylated hydroxytoluene on selected immune surveillance parameters in rats bearing enzyme-altered hepatic preneoplastic lesions.
Selected immune function parameters were examined in male Fischer 344 rats following (a) induction of enzyme-altered preneoplastic liver foci (EAF), and (b) growth modulation of EAF by 30-day feeding with the food antioxidant butylated hydroxytoluene (BHT). Glutathione S-transferase-P (GSTP)-positive EAF were observed in livers of rats receiving diethylnitrosamine (DEN), 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH) (Solt-Farber procedure), with or without BHT treatment. The induction of EAF and/or 0.5% BHT treatment resulted in a significant reduction in the natural killer (NK) cell activity of splenocytes. PH did not affect NK activity significantly compared with control (no PH) rats. The concanavalin A-induced lymphoproliferative activity of splenocytes was increased in rats with PH compared with those without. A lag in time needed to attain maximum calcium release was observed only in the rats with PH compared with those without PH. None of the treatments affected the phagocytic activity of resident peritoneal macrophages. Only EAF-bearing rats without BHT treatment had increased granulocyte and monocyte levels, while the leucocyte and lymphocyte levels were reduced by the initiator DEN. but not by BHT treatment. Further investigations are necessary to determine whether the observed suppression of NK cell activity during EAF induction and growth modulation by BHT is a contributing factor in enhancement of rodent liver neoplasia by this non-genotoxic food antioxidant.
Tryphonas
H
H
Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Protection Branch, Health Canada, Ottawa, Ontario.
Lacroix
F
F
Lok
E
E
Jee
P
P
Clayson
D B
DB
Hayward
S
S
Miller
D
D
Mehta
R
R
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004032:Diet; D005122:Exudates and Transudates / Q000201:enzymology / Q000276:immunology; D005520:Food Preservatives / Q000494:pharmacology*; D006498:Hepatectomy; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010529:Peritoneal Cavity / Q000166:cytology; D010587:Phagocytosis / Q000187:drug effects; D011230:Precancerous Conditions / Q000201:enzymology* / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000276:immunology
D005520:Food Preservatives; D002084:Butylated Hydroxytoluene; D002118:Calcium