Shigenori Minami

The Promoting Effects of Food Dyes, Erythrosine (Red 3) and Rose Bengal B (Red 105), on Thyroid Tumors in Partially Thyroidectomized N‐Bis(2‐hydroxypropyl)‐ nitrosamine‐treated Rats

The effects of erythrosine (Red 3), rose bengal B (Red 105) and thyroidectomy on the development of thyroid tumor were examined in male Wistar rats treated with N‐bis(2‐hydroxypropyl)nitrosamine (DHPN). Red 3 and Red 105 were used at 4% in the basal diet and were administered for 19 weeks from week 2 to 20. Thyroidectomy was performed by resection of the left lobe at week 4. Single injection of DHPN was performed intraperitoneally at 280 mg per 100 g body weight at the beginning of the experiment. Red 3 and Red 105 significantly promoted the development of thyroid tumors in thyroidectomized rats given DHPN, but had no significant effect in non‐thyroidectomized rats. The incidence of thyroid tumors was 91% in rats with partial thyroidectomy, Red 3 and DHPN, 100% in rats with partial thyroidectomy, Red 105 and DHPN, and 64% in rats with partial thyroidectomy and DHPN. Serum TSH was 5.5±3.1 ng/ml in rats with partial thyroidectomy, Red 3 and DHPN, 2.1 ± 2.2 ng/ml in rats with partial thyroidectomy, Red 105 and DHPN, and 1.5±0.5 ng/ml in rats with partial thyroidectomy and DHPN.

Promoting effect of 2,4-diaminoanisole sulfate on rat thyroid carcinogenesis

Two experiments were conducted to examine the effects of 2,4-diaminoanisole sulfate (2,4-DAAS) on thyroid function and carcinogenesis in male Wistar rats. In experiment 1, feeding with 2,4-DAAS resulted in significantly elevated levels of thyroid stimulating hormone (TSH), reduced thyroxine (T4) and triiodothyronine (T3) in the serum, although the latter had almost recovered to normal levels by week 6. However, skin application did not affect serum levels. In experiment 2, administration of 0.5% 2,4-DAAS in the diet for 19 weeks, a week after a single 210 mg/100 g body weight i.p. injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN), significantly increased the incidence and numbers of preneoplastic lesions (focal hyperplasia), adenomas and carcinomas developing in the thyroid gland. Histologically, brown pigment was usually observed within follicular epithelial cells in non-tumorous regions, but not in the tumors themselves.

Effects of trisodium nitrilotriacetate monohydrate, nitrilotriacetic acid and ammonium chloride on urinary bladder carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl) nitrosamine

The effects of trisodium nitrilotriacetate monohydrate (Na3 NTA.H2O) nitrilotriacetic acid (H3NTA) and ammonium chloride (NH4Cl) on two-stage urinary bladder carcinogenesis were examined. Carcinogenesis was initiated by administration of 0.2% N-bis (2-hydroxypropyl)-nitrosamine (DHPN) to male Wistar rats in the drinking water for 2 weeks, and then the animals were treated with basal diet containing Na3NTA.H2O, Na3NTA.H2O plus NH4Cl, H3NTA, H3NTA plus NH4Cl, or without these chemicals for 28 weeks. Na3NTA.H2O increased significantly the resultant incidence of neoplastic and preneoplastic lesions of the urinary bladder. Moreover, treatment with Na3NTA.H2O, without the initiation, itself induced papillary or nodular (PN)-hyperplasia. H3NTA produced only a slight increase in the incidence of preneoplastic urinary bladder lesions (PN-hyperplasia) in rats initiated by DHPN, and this was not statistically significant. Elevation of both pH and sodium ion concentration in the urine were correlated with promotion of tumor development. These data showed that Na3NTA.H2O was more effective than H3NTA with regard to promoting potential, and that changes in both urinary pH and concentration of sodium played important roles in enhancement of urinary bladder tumorigenesis by these chemicals.