Inhibitory effect of probucol on benzo[a]pyrene induced lung tumorigenesis.
The effects of probucol, a clinically used cholesterol lowering and antioxidant drug, on benzo[a]pyrene (B[a]P) induced pulmonary and forestomach tumorigenesis as well as induction of colonic aberrant crypt foci (ACF) in female A/J mice was investigated. Diet containing 1% probucol fed prior to, during and after 8 bi-weekly 1 mg/mouse oral intubations of B[a]P, reduced the number of pulmonary adenomas by 52% (P < 0.001) and the number of forestomach tumors by 31%. The 0.06% probucol diet also resulted in decreased tumor formation but the differences did not reach statistical significance. Both probucol diets significantly reduced the numbers of large ACF, putative preneoplastic lesions of the colon mucosa, but showed no effects on the total numbers of ACF. The results of this study suggest that probucol may also be useful as a chemopreventive agent, in addition to being a cholesterol lowering and anti-atherogenic drug with low toxicity.
Zarkovic
M
M
Department of Pathology, Faculty of Medicine, University of Tokyo, Japan.
Qin
X
X
Nakatsuru
Y
Y
Zhang
S
S
Yamazaki
Y
Y
Oda
H
H
Ishikawa
T
T
Ishikawa
T
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001564:Benzo(a)pyrene; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002784:Cholesterol / Q000097:blood; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008805:Mice, Inbred A; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D011341:Probucol / Q000494:pharmacology*; D012016:Reference Values; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D000924:Anticholesteremic Agents; D002273:Carcinogens; D001564:Benzo(a)pyrene; D002784:Cholesterol; D011341:Probucol