TUMOR-INITIATING ACTIVITY AND CARCINOGENICITY OF DIBENZO[A,L]PYRENE VERSUS 7,12-DIMETHYLBENZ[A]ANTHRACENE AND BENZO[A]PYRENE AT LOW-DOSES IN MOUSE SKIN
TUMOR-INITIATING ACTIVITY AND CARCINOGENICITY OF DIBENZO[A,L]PYRENE VERSUS 7,12-DIMETHYLBENZ[A]ANTHRACENE AND BENZO[A]PYRENE AT LOW-DOSES IN MOUSE SKIN
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DOI：
10.1093/carcin/14.5.875
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发表时间：
1993-05-01
期刊：
影响因子：
4.7
通讯作者：
CAVALIERI, EL
中科院分区：
文献类型：
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作者：
HIGGINBOTHAM, S;RAMAKRISHNA, NVS;CAVALIERI, EL
二苯并[a,l]芘 (DB[a,l]P) 是一种极强的致癌物质，可能存在于环境样品中。通过起始-促进和重复应用在小鼠皮肤中以低剂量进行剂量反应研究，以将其活性与7,12-二甲基苯并[a]蒽（DMBA）、苯并[a]芘（B[a]P）、DB[a,l]P-8,9-二氢二醇和DB[a,l]P-11,12-二氢二醇的活性进行比较。雌性 SENCAR 小鼠用 1 或 0.25 nmol DB[a,1]P、DMBA、B[a]P 或 DB[a,1]P-11,12-二氢二醇启动，并用佛波醇酯乙酸酯促进。在q nmol时，DB[a,l]P诱导2.6个肿瘤/小鼠，而DB[a,1]P-11,12-二氢二醇和DMBA分别诱导0.17个和0.29个肿瘤/小鼠。在低剂量下，DB[a,l]P 诱导 0.79 个肿瘤/小鼠，但其他两种化合物几乎没有活性。仅在 1 nmol 浓度下测试的 B[a]P 没有活性。这三种化合物以及 DB[a,1]P-8,9-二氢二醇通过每周两次重复施用 40 周（每次剂量 1 和 4 nmol）进行测试。此外，还测试了 8 nmol 的 DB[a,l]P、DMBA 和 B[a]P。 8 和 4 nmol 的 DB[a,l]P 分别诱发 91% 和 70% 的小鼠发生恶性肿瘤。 4 nmol 的 DB[a,l]P-11,12-二氢二醇仅在 36% 的小鼠中引发良性肿瘤。 4 nmol DMBA 在一只小鼠中诱导了两种癌症，而在 8 nmol 时，它诱导了一种乳头状瘤和一种皮脂腺腺瘤。 B[a]P 和 DB[a,l]P-8,9-二氢二醇在所有测试剂量下均无活性。这些结果表明，DB[a,l]P 是一种比 DMBA 更有效的致癌物质，DMBA 是以前被认为最有效的芳香烃。将这些结果与之前较高剂量的 DB[a,l]P、DB[a,l]P-11,12-二氢二醇、DMBA 和 B[a]P 的比较相结合 (E.L.Cavalieri 等人 (1991) Carcinogenesis, 12, 1939-1944) 清楚地表明毒性对 DB[a,l]P 及其致瘤性的干扰。 11,12-二氢二醇。
Dibenzo[a,l]pyrene (DB[a,l]P) is an extremely potent carcinogen that may be present in environmental samples. Dose - response studies were conducted at low doses in mouse skin by initiation-promotion and repeated application to compare its activity to that of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B[a]P), DB[a,l]P-8,9-dihydrodiol and DB[a,l]P-11,12-dihydrodiol. Female SENCAR mice were initiated with 1 or 0.25 nmol of DB[a,l]P, DMBA, B[a]P or DB[a,l]P-11,12-dihydrodiol and promoted with phorbol ester acetate. At q nmol, DB[a,l]P induced 2.6 tumors/mouse, whereas DB[a,l]P-11,12-dihydrodiol and DMBA induced 0.17 and 0.29 tumors/mouse respectively. At the low dose, DB[a,l]P induced 0.79 tumors/mouse, but the other two compounds were virtually inactive. B[a]P, tested only at 1 nmol, was inactive. These three compounds, as well as DB[a,l]P-8,9-dihydrodiol, were tested by repeated application twice weekly for 40 weeks at 1 and 4 nmol per dose. In addition, DB[a,l]P, DMBA and B[a]P were also tested at 8 nmol. At 8 and 4 nmol, DB[a,l]P induced malignant tumors in 91 and 70% of mice respectively. At 4 nmol DB[a,l]P-11,12-dihydrodiol elicited only benign tumors in 36% of mice. At 4 nmol DMBA induced two carcinomas in one mouse and at 8 nmol it induced one papilloma and one sebaceous gland adenoma. B[a]P and DB[a,l]P-8,9-dihydrodiol were inactive at all doses tested. These results demonstrate that DB[a,l]P is a much more potent carcinogen than DMBA, the aromatic hydrocarbon previously considered to be the most potent. Combination of these results with previous comparisons of DB[a,l]P, DB[a,l]P-11,12-dihydrodiol, DMBA and B[a]P at higher doses (E.L.Cavalieri et al. (1991) Carcinogenesis, 12, 1939-1944) shows clearly the interference of toxicity with the tumorigenicity of DB[a,l]P and its 11,12-dihydrodiol.