Suppression of diethylnitrosamine-initiated preneoplastic foci development in the rat liver by combined administration of four antioxidants at low doses.
Potential synergism between 4 antioxidants acting at low doses on development of glutathione S-transferase placental form (GST-P)-positive liver cell foci was examined in male rats initially given diethylnitrosamine (200 mg/kg, i.p.). Beginning 2 weeks after the initiation, rats received the antioxidants, individually or in combination, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. The numbers and areas of GST-P-positive foci were significantly decreased by single treatment with butylated hydroxyanisole (BHA, 1%), tert-butylhydroquinone (TBHQ, 1%) and catechol (0.8%), but not with sesamol (0.5%). Combined treatments (BHA + TBHQ, catechol + sesamol, or all 4 chemicals) at a quarter of the above dose levels resulted in decrease in numbers and areas of foci to levels less than the sums of individual inhibition data obtained with the one-quarter levels. Although these combined effects were not statistically significant in the additive model, the results indicate possible synergistic suppression of carcinogenesis by low-dose combined treatment with anti-cancer agents and the usefulness of the present protocol for this type of analysis.
Hasegawa
R
R
First Department of Pathology, Nagoya City University Medical School.
Tiwawech
D
D
Hirose
M
M
Takaba
K
K
Hoshiya
T
T
Shirai
T
T
Ito
N
N
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D052117:Benzodioxoles; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002083:Butylated Hydroxyanisole / Q000627:therapeutic use; D002396:Catechols / Q000627:therapeutic use; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000032:analysis / Q000187:drug effects; D006873:Hydroquinones / Q000627:therapeutic use; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
D000975:Antioxidants; D052117:Benzodioxoles; D002396:Catechols; D006873:Hydroquinones; D010636:Phenols; D002083:Butylated Hydroxyanisole; D004052:Diethylnitrosamine; C025583:sesamol; C018855:2-tert-butylhydroquinone; D005982:Glutathione Transferase; D001973:Bromodeoxyuridine; C034221:catechol