Comparison of the effects of 3-isobutyl-1-methylxanthine and adenosine cyclic 3':5'-monophosphate on the induction of skin tumors by the initiation-promotion protocol and by the complete carcinogenesis process.
Comparison of the effects of 3-isobutyl-1-methylxanthine and adenosine cyclic 3':5'-monophosphate on the induction of skin tumors by the initiation-promotion protocol and by the complete carcinogenesis process.
复制标题
比较 3-异丁基-1-甲基黄嘌呤和环 3:5-单磷酸腺苷对启动-促进方案和完整致癌过程诱导皮肤肿瘤的影响。
DOI：
10.1093/carcin/3.1.53
复制
发表时间：
1982
期刊：
影响因子：
4.7
通讯作者：
Boutwell,RK
中科院分区：
文献类型：
--
作者：
Perchellet,JP;Boutwell,RK
在用8.5nmol的12-O-十四烷酰佛波醇-13-乙酸酯（TPA）促进之前，在小鼠的起始皮肤上局部应用5 μmol的3-异丁基-1-甲基黄嘌呤（IBMX）或0.25 μmol的腺苷环3 '：5' -单磷酸（cAMP），可抑制乳头状瘤和癌的形成。包括IBMX和环AMP在内的联合治疗导致TPA促进的皮肤乳头状瘤和癌的发病率增加。观察到IBMX和cAMP降低肿瘤发生率与其抑制TPA刺激的多胺、RNA、蛋白质和DNA合成之间存在良好的相关性。由于在用单次亚致癌剂量的7，12-二甲基苯并[a]蒽（DMBA）开始之前或之后用这些试剂重复治疗并没有显著改变皮肤肿瘤的发展（Curtiset等人; Perchellet和Boutwell），目前的结果表明，在两步启动-促进方案中，IBMX和环AMP处理可以特异性地降低皮肤致癌的促进刺激。相同剂量的IBMX和环AMP抑制多胺的积累和DMBA处理的皮肤中观察到的大分子合成的增加，但它们对DMBA诱导的皮肤致癌作用的影响取决于所使用的协议和致癌物的剂量。IBMX和cAMP处理不能抑制每周应用0.2 μmol DMBA诱导的皮肤肿瘤。与cAMP处理的抑制作用相反，IBMX增强了对3.6 μmol DMBA单次局部应用的致癌反应。这些药物对DMBA致癌性的相反作用与它们对DMBA诱导的体外程序外DNA合成的不同改变密切相关。环AMP（0.5 mM）增强，而IBMX（0.5 mM）抑制，DMBA诱导的标记前体掺入DNA的分离的表皮细胞在孵育过程中，在存在的羟基脲。因此，它是建议，不同的调制DMBA致癌IBMX和环AMP可能会导致共同作用的致癌物质的启动和促进成分。
Topical application of either 5 μmol of 3-isobutyl-1-methylxanthine (IBMX) or 0.25 μmol of adenosine cyclic 3':5' -monophosphate (cyclic AMP) to the initiated skin of the mouse prior to each promotion with 8.5 nmol of 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited the formation of papillomas and carcinomas. Combined treatments including IBMX and cyclic AMP caused additive reduction of the incidence of skin papillomas and carcinomas promoted by TPA. A good correlation was observed between the reduction of the tumor incidence by IBMX and cyclic AMP and their inhibition of TPA-stimulated polyamine, RNA, protein, and DNA synthesis. Since repeated treatments with these agents before or after initiation with a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene (DMBA) did not alter significantly the development of skin tumors (Curtiset al.; Perchellet and Boutwell), the present results suggest that, in the two-step initiation-promotion protocol, both IBMX and cyclic AMP treatments may decrease specifically the promoting stimulus of skin carcinogenesis. The same doses of IBMX and cyclic AMP inhibited the accumulation of polyamines and the increase in macromolecular synthesis observed in DMBA-treated skin, but their effect on DMBA-induced skin carcinogenesis was dependent upon the protocol used and the dose of carcinogen applied. IBMX and cyclic AMP treatments failed to inhibit the induction of skin tumors by weekly applications of 0.2 μmol of DMBA. In contrast to the inhibitory effect of cyclic AMP treatment, IBMX enhanced the carcinogenic response to a single topical application of 3.6 μmol of DMBA. The opposite effects of these agents on the carcinogenicity of DMBA correlated well with their different alteration of DMBA-induced unscheduled DNA synthesisin vitro. Cyclic AMP (0.5 mM) enhanced, whereas IBMX (0.5 mM) inhibited, the DMBA-induced incorporation of labeled precursor into DNA of isolated epidermal cells during incubation in the presence of hydroxyurea. Therefore, it is suggested that the different modulation of DMBA carcinogenesis by IBMX and cyclic AMP may result from concomitant effects on both the initiating and promoting components of the carcinogen.