Inhibitory effects of the natural products indole-3-carbinol and sinigrin during initiation and promotion phases of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.
The modifying effects of indole-3-carbinol (I3C) and sinigrin (SIN) on the initiation and post-initiation phases of tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4-NQO) were investigated in male ACI/N rats. Rats were divided into eight groups: group 1 was given 4-NQO (10 ppm) in the drinking water for 12 weeks, starting at 7 weeks of age; groups 2 and 3 were given 4-NQO and fed the diets containing I3C (1,000 ppm) and SIN (1,200 ppm) for 14 weeks, respectively, starting at 6 weeks of age; groups 4 and 5 were given 4-NQO and then they were fed I3C and SIN containing diets for 23 weeks, respectively, starting one week after 4-NQO exposure; groups 6 and 7 were given I3C and SIN alone, respectively, during the experiment; group 8 served as an untreated control. At the termination of the experiment (week 37), the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) in group 2 (1/15, 7%), group 3 (1/15, 7%), group 4 (3/15, 20%) or group 5 (2/15, 13%) was significantly smaller than that in group 1 (12/17, 71%) (P = 0.0003, P = 0.005 or P = 0.002). No tongue carcinomas developed in rats of groups 2, 3, and 5. Similarly, the incidence of preneoplastic lesions (hyperplasia and dysplasia) of the tongue in group 2 (11/15, 73%), group 3 (10/15, 67%), group 4 (11/15, 73%) or group 5 (10/15, 67%) was significantly lower than that in group 1 (17/17, 100%) (P = 0.04 or P = 0.02). There were no tongue neoplasms in rats of groups 6, 7, and 8. Administration of I3C and SIN also caused significant decreases in the number and area of silver-stained nucleolar organizer regions protein (AgNORs), a new cell proliferation index, of tongue squamous epithelium. Thus, I3C and SIN inhibited rat tongue carcinogenesis in both the initiation and post-initiation phases, when administered in these respective phases together with, or following treatment with, 4-NQO.
Tanaka
T
T
First Department of Pathology, Gifu University School of Medicine.
Kojima
T
T
Morishita
Y
Y
Mori
H
H
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005961:Glucosinolates / Q000494:pharmacology*; D006965:Hyperplasia; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011912:Rats, Inbred ACI; D014059:Tongue / Q000187:drug effects / Q000473:pathology*; D014062:Tongue Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D005961:Glucosinolates; D007211:Indoles; C010330:sinigrin; D015112:4-Nitroquinoline-1-oxide; C016517:indole-3-carbinol