INHIBITION OF BREAST CARCINOGENESIS BY DIBENZOYLMETHANE

二苯甲酰甲烷抑制乳腺癌的发生

• 批准号: 2733204
• 负责人: MOU-TUAN HUANG
• 金额: $ 18.7万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733204
• 关键词: antineoplastics; athymic mouse; benzanthracenes; breast neoplasms; carcinogen testing; chemical carcinogen; chemical carcinogenesis; chemoprevention; drug interactions; drug metabolism; estradiol; estrogen receptors; gene mutation; liver metabolism; methane; mutagen testing; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; nutrition related tag; ovariectomy; receptor binding; tissue /cell culture

Preliminary studies from this laboratory indicated that feeding 1% dibenzoylmethane (DBM) in the diet has an exceptionally potent inhibitory effect on 7,12 dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sencar mice. Feeding 1% DBM in the diet to C3H/OuJ mice completely (100%) inhibits estrogen-dependent formation of spontaneous breast tumors. In additional studies, feeding 1% DBM in the diet to intact female Sencar mice inhibits proliferation of the mammary gland and uterus as determined by the bromodeoxyuridine (BrdUr) labeling index and uterine wet weight during the estrous phase of the estrous cycle. Additional preliminary studies indicate that feeding 1% DBM in the diet to mice induces increased levels of hepatic cytochromes P-450 as well as increased hepatic hydroxylation and glucuronidation of estradiol. We plan to confirm our preliminary data and to test the hypothesis that DBM inhibits DMBA-induced breast carcinogenesis and spontaneous breast carcinogenesis by antagonizing estrogen action at receptor levels and by inducing phase I and phase II enzymes for carcinogen and estrogen metabolic inactivation. We also plan to test our hypothesis that dietary DBM will inhibit the growth of estrogen-inactivation. We plan to t est our hypothesis that dietary DBM will inhibit the growth of estrogen- dependent breast tumors in Balb/c athymic mice. Our Specific Arms are: (1) to study the dose-response effects of DBM on DMBA-induced mammary carcinogenesis and spontaneous breast cancer in mice and to determine the effects of DBM when it is given at different stages of carcinogenesis (during the initiation, the post initiation or during the growth of breast tumors), (2) to elucidate the effects of dietary DBM on the estradiol mitogenic action and estradiol metabolism, and the effect of DBM as a potential inhibitor of estradiol binding to its receptors will also be evaluated, (3) to elucidate the effects of dietary DBM as a potential inhibitor of estradiol binding to its receptors will also be evaluated, (3) to elucidate the effects of dietary DBM on the formation of mammary gland DNA-[3H]DMBA adducts and DMBA metabolism by liver microsomes. Our proposed studies will provide information on the potency of dietary DBM and on the mechanisms of its inhibitory action on chemically-induced breast carcinogenesis and the formation of spontaneous breast cancer in mice. This project should also provide information on whether or not DBM could be a potentially valuable agent for breast cancer prevention as well as for possible effects on breast cancer growth.

该实验室的初步研究表明，饲喂 1% 饮食中的二苯甲酰甲烷 (DBM) 具有极强的抑制作用 对 7,12 二甲基苯并[a]蒽 (DMBA) 诱导的乳腺的影响 雌性 Sencar 小鼠的致癌作用。 在日粮中添加 1% DBM C3H/OuJ 小鼠完全（100%）抑制雌激素依赖性的 自发性乳腺肿瘤。 在其他研究中，在培养基中添加 1% DBM 完整雌性 Sencar 小鼠的饮食抑制乳腺增殖 通过溴脱氧尿苷 (BrdUr) 标记确定腺体和子宫 发情期动情指数和子宫湿重 循环。 其他初步研究表明，添加 1% DBM 小鼠的饮食会导致肝细胞色素 P-450 水平升高 以及雌二醇的肝脏羟基化和葡萄糖醛酸化增加。 我们计划确认我们的初步数据并检验以下假设： DBM 抑制 DMBA 诱导的乳腺癌发生和自发性乳腺癌 通过在受体水平拮抗雌激素作用和通过 诱导致癌物和雌激素的 I 相和 II 相酶 代谢失活。 我们还计划检验我们的假设，即饮食 DBM会抑制雌激素的生长失活。 我们计划测试 我们的假设是膳食 DBM 会抑制雌激素的生长 Balb/c 无胸腺小鼠的依赖性乳腺肿瘤。 我们的具体工作是： (1) 研究 DBM 对 DMBA 诱导小鼠乳腺癌发生和自发性乳腺癌 并确定在不同阶段给予 DBM 的效果 致癌作用（在发生过程中、发生后或发生过程中） 乳腺肿瘤的生长），（2）阐明膳食 DBM 的影响 对雌二醇促有丝分裂作用和雌二醇代谢的影响 DBM 作为雌二醇与其受体结合的潜在抑制剂将 还进行了评估，(3) 阐明膳食 DBM 作为 雌二醇与其受体结合的潜在抑制剂也将是 评估，（3）阐明膳食 DBM 对形成的影响 乳腺DNA-[3H]DMBA加合物和肝脏对DMBA的代谢 微粒体。 我们提出的研究将提供有关饮食功效的信息 DBM及其对化学诱导的抑制作用机制 乳腺癌的发生和自发性乳腺癌的形成 老鼠。 该项目还应提供有关 DBM 是否 也可能是预防乳腺癌的潜在有价值的药物 至于对乳腺癌生长的可能影响。