The uptake of cystine in isolated rat hepatocytes was enhanced after incubation of the cells with sulfobromophthalein. The enhancement was time- and dose-dependent, with a lag of about 6 hr, and an approximately 4-fold increase in the activity occurred after 24 hr with 0.2 mM sulfobromophthalein. Actinomycin D or cycloheximide completely blocked the time-related increase in the uptake. The enhanced activity of cystine uptake was almost entirely Na+-independent and inhibited by some anionic amino acids, such as glutamate. The uptake of glutamate was also enhanced by sulfobromophthalein. It is concluded that sulfobromophthalein induces the activity of the Na+-independent, anionic amino acid transport system (System x-c) which mediates the transport of cystine. Some other electrophilic agents also enhanced the cystine uptake. The glutathione level of hepatocytes was rapidly reduced by sulfobromophthalein to about 10% of the control level at 6 hr, but at 12 hr it began to rise. It seems likely that this restoration resulted from the induced activity of the cystine uptake because inhibitors of the cystine uptake blocked the restoration and because the uptake of other sulfur amino acids was not enhanced significantly by sulfobromophthalein. System x-c may thus participate in the detoxication of electrophilic agents in hepatocytes.

Animals↗

PubMedDate not supplied

Effects of various steroids on in vitro lifespan and cell growth of human fetal lung fibroblasts (WI-38).

Human fetal lung fibroblasts, WI-38, were cultivated in a medium containing various steroids. A dose-response curve constructed by counting the number of cells on day 16, or at regular intervals, showed that glucocorticoids (hydrocortisone and cortisone) and mineralocorticoids (aldosterone and deoxycorticosterone) caused an increase in cell density when added at physiological concentrations or higher. On the other hand, androgens (testosterone, dihydrotestosterone, and dehydroepiandrosterone), estrogen (17 beta-estradiol), and progesterone caused a decrease in cell density at higher concentrations (5 micrograms/ml, or more) although these had no effect on cell density at concentrations lower than 0.5 micrograms/ml. With cells grown from population doubling 31 in a medium containing steroids, it was shown that hydrocortisone extended the in vitro lifespan of WI-38 cells at concentrations of both 5 micrograms/ml and 0.5 micrograms/ml, while dehydroepiandrosterone, 17 beta-estradiol, and progesterone caused a shortening in lifespan at only 5 micrograms/ml. These results suggest that there is a direct relationship between the effects of steroids on cell growth and the lifespan of human fetal lung fibroblasts.

Aldosterone↗

PubMedDate not supplied

Personal exposure and health effect relationship for NO2 with urinary hydroxyproline to creatinine ratio as indicator.

Establishment of an exposure-effect relationship was attempted between personal nitrogen dioxide (NO2) exposure and urinary hydroxyproline to creatinine ratio of approximately 800 adult women, who were mothers of primary schoolchildren living in two communities around Tokyo. Daily average of the personal NO2 exposure (ENO2) was measured during wintertime by a newly developed personal monitor exposed for 24 hours. The hydroxyproline to creatinine ratio (HOP:C) in the urine sample collected early in the morning of the day for ENO2 measurement was used as a biochemical indicator of the health effect of NO2 exposure. The HOP:C was found to have significant correlation with ENO2 and number of cigarettes smoked actively and passively. ENO2, however, had no correlation with the intensity of the smoking levels; they might affect HOP:C independently. Stepwise multiple regression analysis revealed that HOP:C could be predicted by ENO2 and smoking habits at a high confidence level. The regression analysis of the active smokers' group indicated that a few cigarettes was enough to increase the HOP:C, while in the case of passive smoking, HOP:C increased proportionally to the number of cigarettes.

Adult↗