Effects of protocatechuic acid, S-methylmethanethiosulfonate or 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone(KYN-54) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary carcinogenesis in mice.
Modifying effects of dietary exposure of protocatechuic acid (PCA), a natural monophenolic compound, S-methylmethanethiosulfonate (MMTS), an organosulfur compound newly isolated from cauliflower, and 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone (KYN-54), a novel retinoidal butenolide compound, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (10 micromol, [corrected] single i.p. injection)-induced pulmonary carcinogenesis were examined in female A/J mice. Each of the test chemicals was given in diets during initiation or post-initiation phases (PCA, 1000 ppm; MMTS, 100 ppm; KYN-54, 200 ppm). All of these which had been proved to be chemopreventive mainly in digestive-organs carcinogenesis did not exert any preventive effect in this model when the incidence or multiplicity of pulmonary tumors (adenomas) of mice given NNK and the test chemical at the termination of the experiment (4 months) was compared to that of mice exposed to the carcinogen alone. In contrast, the multiplicity of lung tumors of mice receiving KYN-54 during the post-initiation phase was significantly larger than of the animals with NNK alone (P < 0.05), showing that KYN-54 has a promoting effect on pulmonary carcinogenesis in mice. These data indicate an organotropic activity of these compounds and suggest that candidate compounds for cancer chemoprevention need to be carefully examined for effectiveness in multiple organs by different models.
Mori
H
H
Department of Pathology, Gifu University School of Medicine, Japan.
Matsunaga
K
K
Tanakamaru
Y
Y
Kawabata
K
K
Yamada
Y
Y
Sugie
S
S
Nishikawa
A
A
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000236:Adenoma / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens; D004354:Drug Screening Assays, Antitumor; D005260:Female; D062385:Hydroxybenzoates / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008741:Methyl Methanesulfonate / Q000627:therapeutic use*; D051379:Mice; D008805:Mice, Inbred A; D009602:Nitrosamines; D012176:Retinoids / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D062385:Hydroxybenzoates; D009602:Nitrosamines; D012176:Retinoids; C009091:protocatechuic acid; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C077240:KYN 54; D008741:Methyl Methanesulfonate; D015107:4-Butyrolactone