Comparison of the effects of acute and subacute treatment of phenobarbital in different strains of mice.
A strain specificity has been demonstrated for the effect of subsequent administration of phenobarbital (PB), in which diethylnitrosamine (DENA)-initiated hepatocarcinogenesis was promoted in C3H mice, inhibited in B6C3F1 (C57BL x C3H) and not affected in C57BL mice. A correlation has been established between the ability of barbiturates and hydantoins to promote tumor formation and their ability to induce liver growth, hepatic DNA synthesis and mixed function oxidase activities. Therefore, we examined in these 3 strains of mice and in C3B6F1 (C3H x C57BL) mice the effect of PB administered in their drinking water for 4 days or 28 days. The liver weight to body weight ratio was increased by PB in all types of mice. Microsomal protein concentrations were increased in C57BL mice after 28 days of treatment, in C3H after both 4 days and 28 days and in B6C3F1 after 4 days of treatment. No effect upon microsomal protein content was observed in C3B6F1 mice. DNA content was increased in C3H mice, both in the 4-day and 28-day treatment groups, while the other strains showed either a decrease or no difference from control. DNA synthesis was elevated in all strains of mice after 4 days of treatment with PB, however, after 28 days of treatment there was either a much reduced increase (C57BL and C3B6F1) or no difference (C3H and B6C3F1) from controls. In all 4 types of mice after 4 and 28 days of treatment, PB increased the concentration of cytochrome P-450, the activity of aminopyrine-N-demethylase (AmDm) and 7-ethoxyresorufin-O-deethylase (ErDe) and the oxidation of testosterone (T). The oxidative metabolites of T were similar in the 4 types of mice.
Lin
E L
EL
Genetic Toxicology Division, U.S. Environmental Protection Agency, Cincinnati, OH 45268.
Klaunig
J E
JE
Mattox
J K
JK
Weghorst
C M
CM
McFarland
B H
BH
Pereira
M A
MA
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000033:anatomy & histology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains / Q000502:physiology*; D008862:Microsomes, Liver / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010634:Phenobarbital / Q000008:administration & dosage*; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
D013739:Testosterone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital