Inhibition by beta-carotene of upper respiratory tumorigenesis in hamsters receiving diethylnitrosamine followed by cigarette smoke exposure.
In recent intervention studies, beta-carotene failed to reduce or even increased the incidence of lung cancers in smokers. In the present investigation, the modifying effects of beta-carotene at various doses on the development of upper respiratory tract tumors were investigated in Syrian hamsters treated with diethylnitrosamine (DEN) and cigarette smoke. A total of 120 male 5-week-old hamsters were divided into 4 groups, each consisting of 30 animals. After a single subcutaneous (s.c.) injection of 100 mg/kg DEN, hamsters in groups 1-4 were respectively administered diets supplemented with beta-carotene at doses of 0.5%, 0.05%, 0.005% or 0% during experimental weeks 1 to 13, and simultaneously exposed to cigarette smoke. The duration of cigarette smoke exposure was 9 min twice a day, 5 days a week. Because of a marked reduction of body weight in group 1, the highest dose of beta-carotene was changed to 0.25% after 10 days. In all groups, epithelial hyperplasias and/or papillomas were induced in the larynx and trachea. However, the incidence and multiplicity of papillomas in group 1 were significantly (P < 0.05) lower than the group 4 values. Moreover, the beta-carotene treatments significantly (P < 0.05 or 0.01) reduced both the incidence and multiplicity of hyperplasias in a dose-dependent manner. The levels of retinol and beta-carotene in the serum, and the retinol level in the liver, were also elevated with dose dependence. Our results thus indicate that beta-carotene inhibits tumorigenesis, even at the high dose of 0.25%, under the present experimental conditions.
Furukawa
F
F
Division of Pathology, National Institute of Health Sciences, Tokyo. furukawa@nihs.go.jp
Nishikawa
A
A
Kasahara
K
K
Lee
I S
IS
Wakabayashi
K
K
Takahashi
M
M
Hirose
M
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D006224:Cricetinae; D004249:DNA Damage; D004052:Diethylnitrosamine / Q000633:toxicity; D007822:Laryngeal Neoplasms / Q000517:prevention & control*; D008297:Male; D008647:Mesocricetus; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014134:Tracheal Neoplasms / Q000517:prevention & control*; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D012906:Smoke; D019207:beta Carotene; D004052:Diethylnitrosamine