Promotion mechanism of phenobarbital and partial hepatectomy in DENA hepatocarcinogenesis cell kinetics effect.
Promotion mechanism of phenobarbital and partial hepatectomy in DENA hepatocarcinogenesis cell kinetics effect.
复制标题
苯巴比妥和部分肝切除对DENA肝癌细胞动力学作用的促进机制
作者：
H. Barbason;C. Rassenfosse;E. Betz
用二乙基亚硝胺（DENA，10 mg·kg ~（-1）/d）喂饲大鼠2、4、6周。停止DENA后一周，动物接受部分肝切除术或苯巴比妥给药。部分肝切除术并没有促进肿瘤转化，除了6周的DENA治疗后。最低限度的苯巴比妥需要达到显着的促进作用，在DENA致癌。过于有限的治疗是无效的，但可以通过延长DENA给药来补偿。当肿瘤结节存在时，苯巴比妥治疗变得不必要。致癌物给药后持续给予苯巴比妥促进肿瘤转化，即使在亚致癌性DENA治疗（2周）后也是如此。它加速了病理演变，增加了肿瘤的发病率。在这些条件下，苯巴比妥增加了癌前细胞比正常细胞的增殖优势。在不同的实验模式中，促进作用与慢性细胞增殖的诱导、对2/3部分肝切除术的快速反应的抑制和肝再生过程中通常存在的有丝分裂昼夜节律有关。它的结论是，促进机制可能包括干扰有丝分裂控制，以保持，很长一段时间，允许癌前细胞的选择性生长和随后的转化的细胞增殖的慢性低水平。
Diethylnitrosamine (DENA, 10 mg kg-1 per day) was fed to rats for 2, 4 and 6 weeks. One week after the cessation of DENA, animals were submitted either to partial hepatectomy or to phenobarbital administration. Partial hepatectomy did not promote neoplastic transformation, except after a 6-week DENA treatment. A minimum of phenobarbital was required to reach a significant promoting effect in DENA carcinogenesis. A too-limited treatment was ineffectual but could be compensated for by prolonged DENA administration. The phenobarbital treatment became unnecessary when neoplastic nodules were present. Phenobarbital continuously given after the carcinogen administration promoted neoplastic transformation even after a subcarcinogenic DENA treatment (2 weeks). It accelerated the pathological evolution and increased the tumour incidence. In these conditions, phenobarbital increased the proliferation advantage of preneoplastic cells over normal cells. In the different experimental modalities, the promoting effect was associated with the induction of chronic cell proliferation, the inhibition of the rapid response to the 2/3 partial hepatectomy and the mitotic circadian rhythm normally present during liver regeneration. It is concluded that the promotion mechanism could consist in disturbing the mitotic control in order to maintain, for a long time, a chronic low level of cell proliferation permitting the selective growth of preneoplastic cells and their subsequent transformation.