EFFECTS OF WEAK OR NON-CARCINOGENIC POLYCYCLIC-HYDROCARBONS ON 7, 12-DIMETHYLBENZ[ALPHA]ANTHRACENE AND BENZO[ALPHA]PYRENE SKIN TUMOR-INITIATION
EFFECTS OF WEAK OR NON-CARCINOGENIC POLYCYCLIC-HYDROCARBONS ON 7, 12-DIMETHYLBENZ[ALPHA]ANTHRACENE AND BENZO[ALPHA]PYRENE SKIN TUMOR-INITIATION
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DOI：
10.1016/s0304-3835(79)80076-2
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发表时间：
1979-01-01
期刊：
影响因子：
9.7
通讯作者：
WEEKS, CE
中科院分区：
文献类型：
--
作者：
SLAGA, TJ;JECKER, L;WEEKS, CE
苯并[e]芘 (B[e]P) 可抑制小鼠 7,12-二甲基苯并[a]蒽 (DMBA) 皮肤肿瘤的发生 84%，而芘和荧蒽则分别抑制 DMBA 发生 50% 和 34%。 B[e]P、芘和荧蒽对苯并[a]芘（B[a]P）皮肤肿瘤的发生没有显着影响或有轻微增强作用。 B[e]P对(.±.)B[a]P-7.β.,8.α.-二醇-9.α.,10.α-环氧化物的引发能力基本上没有影响。作为肿瘤引发剂，B[e]P 在 252 μg/水平时具有非常弱的活性（40 周时每只小鼠 0.4 个乳头状瘤），而在 100 μg 水平时则没有活性。当每周两次以 100 μg 的剂量给药时，B[e]P 在 30 周时诱导每只小鼠 2.1 个乳头状瘤，并且 25% 的小鼠在 40 周时患有癌症。与 B[a]P 相比，B[e]P 致癌活性较弱，每周两次 5 μg 剂量即可诱导类似的肿瘤反应。在 DMBA 开始后，当以 100 μg 的剂量每周两次测试 B[e]P 作为肿瘤促进剂时，它在 30 周时诱导了 4.5 个乳头状瘤/小鼠，在 40 周时诱导了 45% 的癌症发生率，其效果大约是单独使用 B[e]P 的两倍。 B[e]P 显然是一种非常弱的肿瘤引发剂、一种弱的完全致癌剂、一种中等的肿瘤促进剂、当与 B[a]P 一起给予时可能是一种弱的共肿瘤引发剂、当与 DMBA 一起给予时是一种强效的抗肿瘤引发剂。 B[e]P 的抗肿瘤引发和共肿瘤引发作用似乎与其修饰肿瘤引发剂转化为能够与 DNA 共价结合的亲电子中间体的能力有关。 B[e]P能诱导表皮细胞增殖，这可能与其促进能力有关。
Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84%, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34%, respectively. B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. B[e]P had essentially no effect on the initiating ability of (.+-.)B[a]P-7.beta.,8.alpha.-diol-9.alpha.,10.alpha.-epoxide. As a tumor-initiator, B[e]P had very weak activity at a 252 .mu.g/level (0.4 papillomas/mouse at 40 wk) and no activity at 100 .mu.g. When given at a dose of 100 .mu.g twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 wk, and 25% of the mice had carcinomas at 40 wk. B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 .mu.g twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 .mu.g twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 wk and a 45% carcinoma incidence at 40 wk, which was approximately twice as effective as B[e]P alone. B[e]P apparently is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anti-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.