Weiss H S, O'Connell J F, Hakaim A G, Jacoby W T
Proc Soc Exp Biol Med. 1986 Feb;181(2):199-204. doi: 10.3181/00379727-181-42240.
In the two-stage mouse model for skin tumorigenesis with phorbol-12-myristate-13-acetate (PMA) as promoter, topical application of 40 microliters of toluene 2X/week at the initiation/promotion site (the back) reduced the average number of tumors/mouse (ANT/M) to approximately one-fourth that of controls. Control procedure involved initiation of C3H mice with benzo[a]pyrene (BaP) and CD-1 mice with 7,12-dimethylbenz[a]anthracene (DMBA) followed by promotion with from 1 to 5 micrograms PMA in 40 microliters acetone 2X/week. Forty microliters of toluene 2X/week per se was a weak promoter (6-13% of control ANT/M), and produced mild skin irritation at the application site but behavior and body weights were normal. The toluene inhibition of tumorigenesis was not a direct chemical action on PMA since similar effects occurred whether toluene was the vehicle for PMA or whether it was applied up to 1 day before PMA (i.e., prepromotion). Prepromotion with acetone had no effect on tumorigenesis, substantiating its use as control vehicle and suggesting that the toluene inhibition was a specific tissue reaction. The inhibitory effect appeared to be on PMA promotion rather than on initiation since toluene and acetone produced similar numbers of tumors when used as the vehicle for BaP or DMBA in two-stage or BaP in single-stage trials. The inhibition was not permanent since tumorigenesis returned to control rates 2-3 weeks after prepromotion with toluene ceased but promotion with PMA in acetone continued. Toluene may be unique among reported promotion inhibitors in that it is a widely used commercial chemical which sometimes serves as a vehicle in cancer-screening trials. Since its metabolism is reasonably well defined, it may be of value in exploring further the process of tumor promotion.
在以佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）为启动子的皮肤肿瘤发生两阶段小鼠模型中，在起始/促癌部位（背部）每周两次局部涂抹40微升甲苯，使每只小鼠的肿瘤平均数量（ANT/M）降至对照组的约四分之一。对照程序包括用苯并[a]芘（BaP）启动C3H小鼠，用7,12-二甲基苯并[a]蒽（DMBA）启动CD-1小鼠，随后每周两次用40微升丙酮中1至5微克PMA进行促癌。每周两次40微升甲苯本身是一种弱启动剂（对照组ANT/M的6-13%），在涂抹部位产生轻度皮肤刺激，但行为和体重正常。甲苯对肿瘤发生的抑制不是对PMA的直接化学作用，因为无论甲苯是PMA的载体还是在PMA前1天涂抹（即促癌前），都会产生类似效果。用丙酮进行促癌前处理对肿瘤发生没有影响，证实了其作为对照载体的用途，并表明甲苯抑制是一种特异性组织反应。抑制作用似乎是对PMA促癌而非起始阶段，因为在两阶段试验中，当甲苯和丙酮分别作为BaP或DMBA的载体，或在单阶段试验中作为BaP的载体时，产生的肿瘤数量相似。这种抑制不是永久性的，因为在用甲苯进行促癌前处理停止2-3周后，肿瘤发生率恢复到对照水平，但丙酮中PMA的促癌作用仍在继续。甲苯可能是已报道的促癌抑制剂中独一无二的，因为它是一种广泛使用的商业化学品，有时在癌症筛查试验中用作载体。由于其代谢已得到较好定义，它可能在进一步探索肿瘤促癌过程中具有价值。
