Modification by sodium L-ascorbate, butylated hydroxytoluene, phenobarbital and pepleomycin of lesion development in a wide-spectrum initiation rat model.
Rats were treated for 1 week each with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 0.2% N-bis(2-hydroxypropyl)-nitrosamine (DHPN) and 0.2% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water, and then administered diet containing 5% sodium L-ascorbate (Na-AsA), 1% butylated hydroxytoluene (BHT) or 0.05% phenobarbital (PB), or weekly intraperitoneal injections of 2 mg of pepleomycin per kg body weight until week 36. Histopathological examination revealed that all exerted significant modulation effects on tumor development in the various target organs. Na-AsA was found to inhibit liver but promote renal pelvis and bladder carcinogenesis. BHT similarly decreased liver and enhanced bladder lesion development. PB, in contrast promoted hepatocarcinogenesis. However both PB and BHT were associated with increased incidences of adenomas and adenocarcinomas of the thyroid. Thus the wide-spectrum initiation model allowed confirmation of site-specific modification potential and in addition demonstrated potentiation of kidney and bladder carcinogenesis promotion by pepleomycin.
Thamavit
W
W
Department of Pathology, Nagoya City University Medical School, Japan.
Fukushima
S
S
Kurata
Y
Y
Asamoto
M
M
Ito
N
N
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D001835:Body Weight; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D003043:Cocarcinogenesis; D007680:Kidney Neoplasms / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D017663:Peplomycin; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013964:Thyroid Neoplasms / Q000139:chemically induced; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D001761:Bleomycin; D002084:Butylated Hydroxytoluene; D017663:Peplomycin; D001205:Ascorbic Acid; D010634:Phenobarbital