ABSTRACT
The activity of urinary N-acetylamino-transferase was determined by high-performance liquid chromatographic assay of acetylisoniazid and isoniazid after administration of isoniazid to healthy Japanese male and bladder cancer patients in Japan. The healthy subjects were 47 college students and 44 company employees ranging from 18 to 64 years old (mean +/- SC = 34.5 +/- 13.7). The bladder cancer group consisted of 58 male and 13 female patients, ranging from 28 to 82 years old (mean +/- SD = 60.8 +/- 11.6), who were being treated at several hospitals. The slow phenotype, defined as an acetylation ratio (acetylisoniazid/isoniazid) of less than 2.0, was observed in 13 (14.3%) of the 91 healthy subjects, and in 20 (28.2%) of the 71 bladder cancer patients; the difference between the two groups is significant (p < 0.05). A histogram of the acetylation ratio values showed an overall leftward shift of the patient group, indicating low values of acetylation ratio in this group as a whole (p < 0.01).
Subject(s)
Arylamine N-Acetyltransferase/urine , Isoniazid/analogs & derivatives , Isoniazid/pharmacokinetics , Urinary Bladder Neoplasms/enzymology , Acetylation , Adolescent , Adult , Aged , Aged, 80 and over , Arylamine N-Acetyltransferase/genetics , Asian People/genetics , Disease Susceptibility/ethnology , Female , Genetic Predisposition to Disease , Humans , Isoniazid/urine , Japan , Male , Middle Aged , Neoplasm Proteins/urine , Occupational Diseases/chemically induced , Occupational Exposure , Phenotype , Smoking , Urinary Bladder Neoplasms/chemically inducedABSTRACT
Consumption of the Agaricus species mushrooms has increased considerably in Japan as the Japanese have become accustomed to Western cooking. The Agaricus species mushroom contains hydrazine derivatives known as Agaritine. Bladder implantation was performed to test the carcinogenic potential of the Agaricus species mushroom which contains large quantities of Agaritine. The results are summarized as follows: 1) Agaritine was detected in fresh Agaricus bisporus mushrooms at the level of 228.2 micrograms/wet weight and in Shiitake (Agaricus edodes) mushrooms at 0.82 microgram/g wet weight, but was not detected in either canned Agaricus bisporus mushrooms or Matsutake (Armillaria edodes) mushrooms. 2) The observed rates of mouse urinary bladder carcinoma were 30.8% for fresh mushrooms (Agaricus bisporus), 23.5% for fresh Shiitake (Agaricus edodes), 9.8% for dry Shiitake, 50% for synthesized Agaritine and 5.4% for paraffin wax as a control. The methanol extract of fresh mushrooms (Agaricus bisporus) and synthesized Agaritine were found to be significantly carcinogenic on the mouse bladder epithelium by the bladder implantation test with a probability of less than 0.01. 3) A large quantity of Agaritine was detected in fresh mushrooms (Agaricus bisporus), but decreased after boiling the mushrooms in water at 100 degrees C for 10 min. 4) The methanol extract of fresh mushrooms (Agaricus bisporus) and synthesized Agaritine are suggested to be the agents for producing cancer in the bladder epithelium. 5) Adding heat to mushrooms containing Agaritine before cooking contributes to the prevention of any potential Agaritine hazard which may induce carcinogenic changes in the bladder epithelium.
Subject(s)
Agaricus/chemistry , Phenylhydrazines/toxicity , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder/drug effects , Animals , Epithelium/drug effects , Epithelium/pathology , Female , Methanol , Mice , Mice, Inbred Strains , Phenylhydrazines/analysis , Plant Extracts/analysis , Plant Extracts/toxicity , Urinary Bladder/pathologyABSTRACT
The genotoxicity of a variety of aniline derivatives was examined by a DNA repair test with rat hepatocytes. Out of 37 aniline derivatives, 6 chemicals, i.e., 2,4,6-trimethylaniline (mesidine), 2,4-xylidine, 3,5-diaminobenzoic acid, 3,4-diaminochlorobenzene, 2-chloro-4-methylaniline and 4-chloro-N-methylaniline, elicited positive DNA repair responses. The results are in agreement with the bacterial mutagenicities with or without norharman of these compounds. Positive compounds of unknown carcinogenicity in the present assay, i.e., 3,5-diaminobenzoic acid, 2-chloro-4-methylaniline and 4-chloro-N-methylaniline are suspected of being potentially carcinogenic.
Subject(s)
Aniline Compounds/pharmacology , DNA Repair/drug effects , Liver/drug effects , Mutagens , Animals , Cells, Cultured , Mutagenicity Tests/methods , Rats , Structure-Activity RelationshipABSTRACT
A high incidence of transitional cell carcinomas were induced in the bladder of mice by bladder implantation of pellets containing crude tryptophan pyrolysate and the pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole (Trp-P-1) and 3-amino-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), which are highly mutagenic substances.
