sinigrin and Precancerous-Conditions

Glucosinolates are sulphur compounds that occur as glycosides in brassica vegetables. In response to tissue disruption they are degraded by thioglucosidase, releasing a range of highly reactive breakdown products, including the isothiocyanates, which we have previously shown to be selectively cytotoxic to undifferentiated colorectal tumour cells (HT29). In the present study we explored the effect of sinigrin on the intestinal mucosa of rats previously treated with dimethylhydrazine (DMH). In the first experiment, a semisynthetic feed containing sinigrin (400 microg/g diet) was provided 6 h after the second of two injections of DMH. The level of apoptosis was measured by morphological assessment of intact microdissected crypts obtained at 18, 24, 38, 48 and 72 h after injection, and compared with control groups given DMH only, or a sham-injection. Higher numbers of apoptotic nuclei were present in colonic tissue from both groups of DMH-treated rats compared with the controls, and the level was significantly higher in DMH-treated rats fed sinigrin compared with those given DMH only (P < 0.02). In a second experiment, rats were given sinigrin (400 microg/g diet) 22 h after the second of two injections of DMH; the level of apoptosis was measured after 48 h and the numbers of aberrant crypt foci (ACF) were measured after 42 days. The level of apoptosis was significantly higher in DMH-treated rats given sinigrin compared with controls (P < 0.05), and the numbers of ACF were significantly lower in sinigrin-treated rats (P < 0.001). There was no statistically significant induction of apoptosis in animals fed sinigrin alone. Sinigrin administered after DMH suppresses induction of ACF. This may be due to increased apoptotic deletion of damaged stem cells in the crypts of animals fed sinigrin.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Colonic Neoplasms; Dimethylhydrazines; Glucosinolates; Intestinal Mucosa; Male; Microscopy, Electron, Scanning; Precancerous Conditions; Rats; Rats, Wistar; Time Factors

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.

Topics: 4-Nitroquinoline-1-oxide; Animals; Anticarcinogenic Agents; Antioxidants; Body Weight; Carcinoma, Squamous Cell; Glucosinolates; Hyperplasia; Indoles; Liver; Male; Organ Size; Papilloma; Precancerous Conditions; Rats; Rats, Inbred ACI; Tongue; Tongue Neoplasms

The modifying effects of sinigrin (Sin) and indole-3-carbinol (I3C) on the hepatocarcinogenesis induced by diethylnitrosamine (DEN) were investigated in male ACI/N rats. Rats were divided into six groups: group 1 was given DEN (40 p.p.m.) in the drinking water for 5 weeks, starting at 7 weeks of age; group 2 was treated with DEN and diet containing 1200 p.p.m. Sin; group 3 received DEN and diet containing 1000 p.p.m. I3C; group 4 was given Sin diet alone; group 5 was given I3C diet alone; and group 6 served as controls. The diet containing Sin or I3C was fed to the rats starting at 6 weeks of age until 1 week after the carcinogen exposure. At termination of the experiment (week 29), the incidences of iron-excluding altered foci (11.22 +/- 3.22/cm2) and liver cell tumors (6/12, 50%) and the tumor multiplicity (0.9/rat) in rats of group 2 were significantly smaller than those of group 1 (foci incidence, 48.33 +/- 6.34/cm2, tumor incidence, 10/10, 100%; multiplicity, 9.5/rat) (P less than 0.02). Similarly, the incidence of iron-excluding hepatocellular foci (17.65 +/- 4.67/cm2) and tumor multiplicity (2.4/rat) with a slight reduction of tumor incidence (9/12, 75%) in rats of group 3 were significantly lower than those of group 1 (P less than 0.001). There were no liver cell neoplasms in rats of groups 4, 5 and 6. Thus, Sin and I3C inhibited the hepatocarcinogenesis induced by DEN when they were administered concurrently with the carcinogen.

Topics: Animals; Diethylnitrosamine; DNA; Glucosinolates; Indoles; Liver Neoplasms, Experimental; Male; Precancerous Conditions; Rats; Rats, Inbred ACI; Thioglycosides