Raunio H, Pelkonen O
Cancer Res. 1983 Feb;43(2):782-6.
Single i.p. injections of 3-methylcholanthrene (MC; 50 mg/kg) administered to inbred C57BL/6 mice or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 100 micrograms/kg) to DBA/2 mice gave an increase in the hepatic activities of ornithine decarboxylase (ODC) and aryl hydrocarbon hydroxylase (AHH) with peaks occurring by 12 and 48 hr, respectively. A single i.p. dose of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 micrograms/kg) enhanced the activity of ODC about 70-fold within 12 hr in C57BL/6 mice and 18-fold within 24 hr in DBA/2 mice without affecting AHH activity markedly. 4-O-Methyl-12-O-tetradecanoylphorbol-13-acetate (100 micrograms/kg) raised ODC activity to about 25% of the TPA-treated value in C57BL/6 mice; in DBA/2 mice, TPA and 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate induced ODC activity to roughly the same level. Benzo(e)pyrene (50 mg/kg) failed to affect ODC and AHH activities significantly in either strain. The inducing effect of TPA on ODC activity was potentiated by a simultaneous administration of MC to C57BL/6 mice; combined TPA and TCDD to DBA/2 mice exerted an additive effect on hepatic ODC activity. Difluoromethylornithine administered i.p. effectively inhibited the induction of ODC activity elicited by TPA, MC, or TCDD either alone or in various combinations but did not interfere with AHH induction. These data indicate that different regulatory factors are involved in the ODC induction process elicited by TPA and polycyclic aromatic compounds and that MC and TCDD may induce ODC activity by different mechanisms. The results also confirm our earlier findings in rat skin and cells in culture which suggest that the ODC and AHH induction processes can occur independently of each other. Additionally, there is a strain-related difference in sensitivity with regard to ODC-inducing activity of TPA in the livers of C57BL/6 and DBA/2 mice.
对近交系C57BL/6小鼠单次腹腔注射3-甲基胆蒽（MC；50毫克/千克）或对DBA/2小鼠单次腹腔注射2,3,7,8-四氯二苯并对二恶英（TCDD；100微克/千克），可使鸟氨酸脱羧酶（ODC）和芳烃羟化酶（AHH）的肝脏活性增加，峰值分别在12小时和48小时出现。单次腹腔注射肿瘤促进剂12-O-十四酰佛波醇-13-乙酸酯（TPA；100微克/千克）可使C57BL/6小鼠在12小时内ODC活性增强约70倍，使DBA/2小鼠在24小时内增强18倍，且对AHH活性无明显影响。4-O-甲基-12-O-十四酰佛波醇-13-乙酸酯（100微克/千克）可使C57BL/6小鼠的ODC活性提高至TPA处理值的约25%；在DBA/2小鼠中，TPA和4-O-甲基-12-O-十四酰佛波醇-13-乙酸酯诱导的ODC活性大致相同。苯并(e)芘（50毫克/千克）对两种品系的ODC和AHH活性均无显著影响。同时给C57BL/6小鼠注射MC可增强TPA对ODC活性的诱导作用；给DBA/2小鼠联合注射TPA和TCDD对肝脏ODC活性有相加作用。腹腔注射二氟甲基鸟氨酸可有效抑制单独或多种组合的TPA、MC或TCDD所引发的ODC活性诱导，但不干扰AHH的诱导。这些数据表明，TPA和多环芳烃化合物引发的ODC诱导过程涉及不同的调节因子，且MC和TCDD可能通过不同机制诱导ODC活性。结果还证实了我们早期在大鼠皮肤和培养细胞中的发现，即ODC和AHH诱导过程可能相互独立发生。此外，C57BL/6和DBA/2小鼠肝脏对TPA的ODC诱导活性存在品系相关的敏感性差异。
