Toxic Effects of Benzyl and Allyl Isothiocyanates and Benzyl-Isoform Specific Metabolites in the Urinary Bladder After a Single Intravesical Application to Rats

Allyl isothiocyanate (AITC) is known to be weakly carcinogenic, whereas benzyl isothiocyanate (BITC) has been suggested to exert carcinogenicity toward the rat urinary bladder. To elucidate direct toxic effects of isothiocyanates (ITCs), BITC, AITC, or BITC-metabolites conjugated either with glutath...

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Bibliographic Details
Published in:Toxicologic pathology 2001-11, Vol.29 (6), p.617-622
Main Authors: Masutomi, Naoya, Toyoda, Kazuhiro, Shibutani, Makoto, Niho, Naoko, Uneyama, Chikako, Takahashi, Noriyuki, Hirose, Masao
Format: Article
Language:English
Subjects:
Acetylcysteine - toxicity
Administration, Intravesical
allyl isothiocyanate
Animals
benzyl isothiocyanate
Biological and medical sciences
Cells, Cultured
Chemical and industrial products toxicology. Toxic occupational diseases
Cysteine - toxicity
Dipeptides - toxicity
Female
Glutathione - toxicity
Isothiocyanates - toxicity
Medical sciences
Rats
Rats, Inbred Strains
Toxicology
Urinary Bladder - drug effects
Urinary Bladder - pathology
Urothelium - drug effects
Urothelium - pathology
Various organic compounds
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Summary:Allyl isothiocyanate (AITC) is known to be weakly carcinogenic, whereas benzyl isothiocyanate (BITC) has been suggested to exert carcinogenicity toward the rat urinary bladder. To elucidate direct toxic effects of isothiocyanates (ITCs), BITC, AITC, or BITC-metabolites conjugated either with glutathione, cysteinylglycine, cysteine, or mercapturic acid were intravesically instilled into female F344 rats. Exposure to AITC and BITC at 2.8 mg/kg body weight, and the same mol quantity (37 μ mol/kg) of BITC-metabolites was for 2 h. Nineteen hours thereafter, the animals were intravenously administered 5-bromo-2'-deoxyuridine (BrdU) and killed 1 h later. BITC caused more profound toxic damage than AITC. Among the BITC-metabolites, cytotoxicity was evident with intermediate glutathione or cysteinylglycine conjugates, whereas the mercapturic acid, considered to be the major final urinary metabolite, exerted little effects. BrdU labeling was essentially dependent on the degree of cytotoxic potential of each compound. Considering the previous study results demonstrating the generation of free BITC from metabolites in urine, the present results support the idea that cytotoxic activity of orally administered ITCs is derived from free forms cleaved from conjugated metabolite(s) in urine.
ISSN:0192-6233
1533-1601
DOI:10.1080/019262301753385942