Alworth W L, Viaje A, Sandoval A, Warren B S, Slaga T J
Department of Chemistry, Tulane University, New Orleans, LA 70118.
Carcinogenesis. 1991 Jul;12(7):1209-15. doi: 10.1093/carcin/12.7.1209.
A single dose of 1-ethynylpyrene (EP), 1-vinylpyrene (VP) or 2-ethynylnaphthalene (EN) was applied to the skin of SENCAR mice 5 min before an initiating dose of 7,12-dimethylbenz[a]anthracene (DMBA) or benzo[a]pyrene (B[a]P) and the development of skin tumors then promoted with biweekly topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). The application of EP strongly inhibited the formation of skin tumors initiated by either DMBA or B[a]P in a dose-dependent manner. Application of 44 pmol of EP inhibited tumor initiation by 10 nmol of DMBA approximately 25%; application of 440 nmol of EP inhibited tumor initiation by 200 nmol of B[a]P approximately 51%. A high single dose of EP (4.4-44 mumol) nearly eliminated skin tumor initiation by either 10 nmol of DMBA or 200 nmol of B[a]P. Application of VP also inhibited the formation of skin tumors initiated by either DMBA or B[a]P in a dose-dependent manner, but higher doses of VP than of EP were required to produce comparable inhibitions. Application of 44 nmol of VP inhibited tumor initiation by 10 nmol of DMBA approximately 30%; application of 4.4 mumol of VP inhibited tumor initiation by 200 nmol of B[a]P approximately 56%. Application of EN yielded contrasting results. EN inhibited the formation of skin tumors initiated by 10 nmol of DMBA, but the observed dose-dependence was minimal; tumors were decreased about 40% by 3.3 mumol of EN and only about 65% by 132 mumol of EN. A high single dose of EN (132 mumol) increased both the mean number of tumors per mouse and the percentage of mice that developed tumors after initiation by 200 nmol of B[a]P. Topical application of 4.4 mumol of EP, 22 mumol of VP or 33 mumol of EN to the skin of SENCAR mice 5 min before a single initiation dose of 2.5 mumol of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) had a minimal inhibitory effect (14-28%) on the development of skin tumors produced by subsequent biweekly promotion with TPA. A single dose of 44 mumol of EP or 132 mumol of EN followed by biweekly applications of TPA did not produce skin tumors; however, a dose of 44 mumol of VP followed by promotion with TPA produced a low but significant number of skin tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
在给予起始剂量的7,12-二甲基苯并[a]蒽（DMBA）或苯并[a]芘（B[a]P）前5分钟，将单剂量的1-乙炔基芘（EP）、1-乙烯基芘（VP）或2-乙炔基萘（EN）涂抹于SENCAR小鼠的皮肤上，随后每两周局部涂抹12-O-十四烷酰佛波醇-13-乙酸酯（TPA）以促进皮肤肿瘤的发生。EP的涂抹以剂量依赖的方式强烈抑制由DMBA或B[a]P引发的皮肤肿瘤的形成。涂抹44 pmol的EP可使10 nmol的DMBA引发的肿瘤起始抑制约25%；涂抹440 nmol的EP可使200 nmol的B[a]P引发的肿瘤起始抑制约51%。高单剂量的EP（4.4 - 44 μmol）几乎消除了由10 nmol的DMBA或200 nmol的B[a]P引发的皮肤肿瘤起始。VP的涂抹也以剂量依赖的方式抑制由DMBA或B[a]P引发的皮肤肿瘤的形成，但需要比EP更高的剂量VP才能产生相当的抑制作用。涂抹44 nmol的VP可使10 nmol的DMBA引发的肿瘤起始抑制约30%；涂抹4.4 μmol的VP可使200 nmol的B[a]P引发的肿瘤起始抑制约56%。EN的应用产生了相反的结果。EN抑制了由10 nmol的DMBA引发的皮肤肿瘤的形成，但观察到的剂量依赖性最小；3.3 μmol的EN使肿瘤减少约40%，132 μmol的EN仅使肿瘤减少约65%。高单剂量的EN（132 μmol）增加了每只小鼠的平均肿瘤数量以及在由200 nmol的B[a]P引发后发生肿瘤的小鼠百分比。在给予单剂量2.5 μmol的N-甲基-N'-硝基-N-亚硝基胍（MNNG）起始剂量前5分钟，将4.4 μmol的EP、22 μmol的VP或33 μmol的EN局部涂抹于SENCAR小鼠的皮肤上，对随后每两周用TPA促进产生的皮肤肿瘤的发展具有最小的抑制作用（14 - 28%）。单剂量44 μmol的EP或132 μmol的EN随后每两周涂抹TPA未产生皮肤肿瘤；然而，44 μmol的VP剂量随后用TPA促进产生了少量但显著数量的皮肤肿瘤。（摘要截短于400字）
