Inhibitory effects of antioxidants on N-bis(2-hydroxypropyl)nitrosamine-induced lung carcinogenesis in rats.
Potential second-stage modifying effects of 8 antioxidants on lung tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were examined in male F344 rats. After an initial 2-week treatment with DHPN (0.1% in drinking water), rats were administered one of the antioxidants supplemented in the diet for 30 weeks. Although the incidences of lung adenomas were not affected, those of carcinomas were lowered by 2% butylated hydroxyanisole (BHA, 2 rats/20 rats), 1% butylated hydroxytoluene (BHT, 1/20), 0.8% ethoxyquin (EQ, 3/20) and 1% a-tocopherol (a-TP, 2/20) treatments as compared to the control level (9/20), while 5% sodium L-ascorbate (SA), 0.8% catechol (CC), 0.8% resorcinol (RN), and 0.8% hydroquinone (HQ) did not exert any significant effect on incidence. Quantitative analysis of adenomas and carcinomas (numbers and areas of lesions per unit area of lung section) revealed obvious inhibitory effects of SA, CC, and RN as well as BHA, BHT, EQ, and a-TP. Among the antioxidants, BHT exerted the strongest inhibitory activity. In contrast, DHPN-induced thyroid tumorigenesis was significantly enhanced by BHT (14/20) and EQ (20/20) treatments (control = 5/20). Thus the antioxidants showed opposite effects on lung and thyroid carcinogenesis in the rat.
Hasegawa
R
R
Division of Pathology, National Institute of Hygienic Sciences, Tokyo.
Furukawa
F
F
Toyoda
K
K
Takahashi
M
M
Hayashi
Y
Y
Hirose
M
M
Ito
N
N
D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002277:Carcinoma / Q000139:chemically induced; D002396:Catechols / Q000494:pharmacology; D005015:Ethoxyquin / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009602:Nitrosamines / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012118:Resorcinols / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000139:chemically induced* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D002396:Catechols; D006873:Hydroquinones; D009602:Nitrosamines; D012118:Resorcinols; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; C012457:diisopropanolnitrosamine; D005015:Ethoxyquin; C034221:catechol; D001205:Ascorbic Acid; C031927:hydroquinone; C031389:resorcinol