Effects of barbiturates with or without liver-tumor-promoting activity on survival and DNA synthesis of suckling and adult rat hepatocytes in serum-free primary culture.
The effects of four barbiturates with or without liver-tumor-promoting activity were examined on survival and deoxyribonucleic acid (DNA) synthesis of suckling and adult rat hepatocytes in serum-free primary culture: Of the four barbiturates, two promoters, phenobarbital and barbital, enhanced DNA synthesis of suckling rat hepatocytes at low concentrations of 0.5-2 mM or 0.5 mM, but suppressed it at high concentrations of 3 mM or 1.5-4 mM. DNA synthesis of adult rat hepatocytes was, however, only suppressed by phenobarbital within the dose range tested of 1-3 mM. On the other hand, two remaining non-promoters, barbituric acid and amobarbital, did not increase but only suppressed DNA synthesis of suckling rat hepatocytes within the dose ranges of 0.5-4 mM and 0.05-0.5 mM respectively. Phenobarbital and amobarbital were effective for supporting survival and maintaining morphological features of suckling and adult rat hepatocytes at the relatively high concentrations of 3-4 mM and 0.5-0.75 mM respectively. However, barbital and barbituric acid were ineffective for maintenance of hepatocytes. The results show that the ability to support survival of primary cultured hepatocytes is not a common property of liver-tumor-promoter barbiturates but is a common property of some barbiturates with high lipophilicity, and that the maintenance of hepatocytes by phenobarbital or amobarbital is not due to a counterbalance of stimulated proliferation and death of the cells.
Miyazaki
M
M
Department of Cell Biology, Okayama University Medical School, Japan.
Bai
L
L
Tsuboi
S
S
Namba
M
M
D000375:Aging; D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D001462:Barbital / Q000494:pharmacology; D001463:Barbiturates / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001463:Barbiturates; D002273:Carcinogens; D016895:Culture Media, Serum-Free; D001462:Barbital; D000654:Amobarbital; C032232:barbituric acid; D010634:Phenobarbital