Abou-Issa H M, Duruibe V A, Minton J P, Larroya S, Dwivedi C, Webb T E
Comprehensive Cancer Center, Ohio State University, Columbus 43210.
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4181-4. doi: 10.1073/pnas.85.12.4181.
Calcium glucarate and N-(4-hydroxyphenyl)retinamide were evaluated individually and in combination in the diet as preventative chemical agents, by using the induction of rat mammary tumors by 7,12-dimethylbenz[a]anthracene as the test system. When tested separately over 18 weeks, optimal doses of calcium glucarate (128 mmol/kg of diet) or N-(4-hydroxyphenyl)retinamide (1.5 mmol/kg of diet) administered daily inhibited tumor incidence by 50% or 57% and tumor multiplicity by 50% or 65%, respectively. Suboptimal doses of calcium glucarate (32 mmol/kg) and of N-(4-hydroxyphenyl)retinamide (0.75 mmol/kg) inhibited tumor incidence by 15% and 5% but had no inhibitory effect on tumor multiplicity. In contrast, the combination of calcium glucarate (32 mmol/kg) and N-(4-hydroxyphenyl)retinamide (0.75 mmol/kg) inhibited tumor incidence and tumor multiplicity by 50%. Similar synergism was observed with the combination of calcium glucarate (64 mmol/kg) and N-(4-hydroxyphenyl)retinamide (0.75 mmol/kg), the inhibition being 55-60%. HPLC analysis of the bile of female rats injected intraperitoneally with a single dose of the retinamide [60 mg/kg (body weight)] showed that the excretion of the retinamide and its glucuronide were markedly suppressed by pretreatment with an oral dose of calcium glucarate [4.5 mmol/kg (body weight)].
以7,12 - 二甲基苯并[a]蒽诱导大鼠乳腺肿瘤作为测试系统，对饮食中单独及联合使用的葡萄糖醛酸钙和N -（4 - 羟基苯基）视黄酰胺作为预防性化学药剂进行了评估。当在18周内分别进行测试时，每日给予最佳剂量的葡萄糖醛酸钙（128 mmol/kg饮食）或N -（4 - 羟基苯基）视黄酰胺（1.5 mmol/kg饮食）可使肿瘤发生率分别降低50%或57%，肿瘤多发性分别降低50%或65%。次优剂量的葡萄糖醛酸钙（32 mmol/kg）和N -（4 - 羟基苯基）视黄酰胺（0.75 mmol/kg）可使肿瘤发生率分别降低15%和5%，但对肿瘤多发性无抑制作用。相比之下，葡萄糖醛酸钙（32 mmol/kg）和N -（4 - 羟基苯基）视黄酰胺（0.75 mmol/kg）联合使用可使肿瘤发生率和肿瘤多发性降低50%。葡萄糖醛酸钙（64 mmol/kg）和N -（4 - 羟基苯基）视黄酰胺（0.75 mmol/kg）联合使用也观察到类似的协同作用，抑制率为55 - 60%。对腹腔注射单剂量视黄酰胺[60 mg/kg（体重）]的雌性大鼠胆汁进行HPLC分析表明，口服葡萄糖醛酸钙[4.5 mmol/kg（体重）]预处理可显著抑制视黄酰胺及其葡萄糖醛酸苷的排泄。
