Induction of mammary gland and skin tumours in female rats by the feeding of benzyl violet 4B

Ikeda, Yoshio; Horiuchi, Shigetomo; Imoto, Akiko; Kodama, Yukio; Aida, Yoshitaka; Kobayashi, Kazuo

doi:10.1016/0300-483x(74)90019-5

Cited by 8 publications

(2 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was concluded that occupational exposure to pararosaniline, a primary arylamine, was associated with increased risks of bladder cancer in dye industry workers (6). Benzyl violet 4B was found to be carcinogenic in several organs in rats (7). MG has been reported to enhance the development of preneoplastic lesions induced in livers from rats treated with N-nitrosodiethylamine (8).…”

Section: Introductionmentioning

confidence: 99%

Mechanism for Inhibition of Thyroid Peroxidase by Leucomalachite Green

Doerge

Chang

Divi

et al. 1998

Chem. Res. Toxicol.

View full text Add to dashboard Cite

The triphenylmethane dye, malachite green (MG), is used to treat and prevent fungal and parasitic infections in the aquaculture industry. It has been reported that the reduced metabolite of MG, leucomalachite green (LMG), accumulates in the tissues of fish treated with MG. MG is structurally related to other triphenylmethane dyes (e.g., gentian violet and pararosaniline) that are carcinogenic in the liver, thyroid, and other organs of experimental animals. The ability of LMG to inhibit thyroid peroxidase (TPO), the enzyme that catalyzes the iodination and coupling reactions required for thyroid hormone synthesis, was determined in this study. LMG inhibited TPO-catalyzed tyrosine iodination (half-maximal inhibition at ca. 10 microM). LMG also inhibited the TPO-catalyzed formation of thyroxine in low-iodine human goiter thyroglobulin (half-maximal inhibition at ca. 10 microM) using a model system that measures simultaneous iodination and coupling. Direct inhibition of the coupling reaction by LMG was shown using a coupling-only system containing chemically preiodinated thyroglobulin as the substrate. Incubation of LMG with TPO, iodide, and tyrosine in the presence of a H2O2-generating system yielded oxidation products that were identified by using on-line LC/APCI-MS as desmethyl LMG, 2desmethyl LMG, 3desmethyl LMG, MG, and MG N-oxide. Similar products from LMG were observed in incubations with TPO and H2O2 alone. These findings suggest that the anti-thyroid effects (increased serum thyroid-stimulating hormone and decreased serum thyroxine) observed in rats treated with LMG result from blockade of hormone synthesis through alternate substrate inhibition and that chronic exposure could cause thyroid follicular cell tumors through a hormonal mechanism. The observed TPO-catalyzed oxidative demethylation of LMG to a primary arylamine also suggests a genotoxic mechanism for tumor formation is possible.

show abstract

Section: Introductionmentioning

confidence: 99%

Mechanism for Inhibition of Thyroid Peroxidase by Leucomalachite Green

Doerge

Chang

Divi

et al. 1998

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…Case and Pearson (1954) noted an increased risk of contracting bladder cancer in industrial workers engaged in manufacturing magenta. Benzyl violet 4B, an alkyl sulfonate derivative of gentian violet, primarily induced tumors of the ear duct and mammary gland in female Sprague-Dawley rats (Ikeda et al, 1974).…”

mentioning

confidence: 99%

Chronic Toxicity and Carcinogenicity Studies of Gentian Violet in Mice

et al. 1985

View full text Add to dashboard Cite

9 12. Gentian violet is a dye belonging to a chemical class known as the di-and triaminophenylmethanes. Although it has been used for many years for the control of fungal and intestinal parasites, for various uses in veterinary medicine, and as an additive to the feed of chickens to inhibit propagation of mold and fungus, very few long-term toxicity data are available. A life span dosing study of gentian violet in the diet of 720 males and 720 females of R6C3Fi mice (C57BL/6 X C3H) at dose levels of 0, 100,300, and 600 ppm was done to determine its toxicity and carcinogenicity. Sacrifices were conducted afler 12, 18, and 24 months of continuous dosing. There was no effect on food consumption or body weight gain; however, a dose effect was noted for mortality rates. Mortality (adjusted for sacrifices) in the controls of both sexes was less than 15% at 24 months, but was approximately 64% in the females and 23% in the males given the high dose. Females appeared to be more susceptible than males. A positive dose response for hepatocellular carcinoma was noted in males at 24 months and in females at 18 and 24 months. Statistical tests for dose-related trends with respect to (1) mortality due to liver neoplasms, (2) prevalence of liver neoplasms, and (3) time to onset of liver neoplasms showed positive trends in both males and females. Other dose-related toxicological responses, particularly in the female mice, included erythropoiesis in the spleen, atrophy of the ovaries, adenoma of the Harderian gland, and the presence of type A reticulum cell sarcomas in the urinary bladder, uterus, ovaries, and vagina. The estimation of risk of 10e6 over background for malignant liver neoplasms using linear extrapolations showed a lower bound on the virtually safe dose (VSD) to be 2 ppb for the female mice and 1 ppb for the male mice. For benign and malignant liver tumors together, the lower bound on the VSD was essentially the same as for malignant liver neoplasm alone. Under the conditions of the experiment described above, gentian violet appears to be a carcinogen in mice at several different organ sites. 0 1985 hi* 0f Toxicology. ' Pathology Associates, Inc., National Center for Tox-Fuji& (1977) has shown gentian violet to icological Research, Jefferson, Ark. 72079. be mutagenic to Bacillus subfilis, Escherichia ' System Development Corp., National Center for Tox-coli, and Salmonella typhimurium. Au et al.

show abstract