To investigate the transforming potency of flavoring agents, Chinese hamster (CH) B241 cells were treated with various concentrations of flavoring agents for 24 hours during their exponential growth period. Surviving cells were cultivated for generations without the agents to observe the appearance of growth properties characteristic of transformed cells. Highly increased rates of structural and numerical chromosome abnormalities were seen in the cells treated with a high concentration of the agents, especially with allylisothiocyanate (AITC) or tr-cinnamic aldehyde (CA). During subsequent passages of the treated cells, the survivors from treatment with sublethal doses of AITC or CA showed a significant increase in cloning efficiency in soft agar medium, especially after passage in soft agar. Also noted was an increase in saturation density in monolayer culture, though a significant increase in plating efficiency at low serum level was not observed. These characteristic changes in AITC- or CA-treated cells were associated with the significant increase in frequencies of cells containing almost 3n to 4n chromosomes.
The effects of p-tert-butylphenyl trans-4-guanidinomethyl cyclohexane carboxylate hydrochloride (NCO-650) on drug-metabolizing enzymes and fine structure in rat liver were investigated. Aminopyrine demethylase, cytochrome b5 and cytochrome P-450 contents increased by a single administration of NCO-650 (10, 100 and 1000 mg/kg, p. o.). NCO-650 caused the morphological changes of liver fine structure such as disarrangement of rough endoplasmic reticulum (rER), detachment of ribosome from the rER and increase in smooth endoplasmic reticulum. The increases in drug-metabolizing enzyme activities and morphological changes in rat liver by NCO-650 were not dose-dependently. Trimethadione metabolism was not accelerated by the administration of NCO-650. In those results, the morphological changes in liver by a single administration of NCO-650 seem to be a direct action on the membrane of hepatocytes and its organelle. The induction of drug-metabolizing enzyme contents by NCO-650 was suggested a transitory response with the morphological changes in the liver.
Behavioral effects of experimental perinatal methylmercury exposure are reviewed. Studies were summarized by classification based on examined behaviors and functions as follows ; 1) Development of reflexive behaviors, 2) Swimming ability, 3) Spontaneous activity, 4) Open-field behavior, 5) Maze learning, 6) Avoidance learning, 7) Operant learning, 8) Susceptibility to induced convulsion and seizure, 9) Ultrasonic vocalization, 10) Visual function. Findings suggest that perinatal methylmercury exposure caused changes in a wide spectrum of behaviors in offspring. It is suggested that further researches on neuro-behavioral teratogenicity of methylmercury will be awaited, especially in the area investigating interaction of the other environmental factors.