Brusick D, Myhr B, Galloway S, Rundell J, Jagannath D R, Tarka S
Mutat Res. 1986 Mar;169(3):105-14. doi: 10.1016/0165-1218(86)90089-3.
Theobromine (3,7-dimethylxanthine) was evaluated for genotoxic activity in a series of in vitro assays. Theobromine was not mutagenic in the Ames assay up to a maximum concentration of 5000 micrograms/plate either with or without S9 activation. The compound also failed to induce significant levels of chromosome aberrations in CHO cells (with and without S9 activation) or transformation in Balb/c-3T3 cells. At the maximum tolerated concentration theobromine increased the frequency of TK-/- mutants in mouse lymphoma L5178Y cells. Increased frequencies were observed both with and without S9 activation and they were reproducible in 2 independent experiments. Statistically significant increases in SCEs were obtained in human lymphocytes and in CHO cells under nonactivation test conditions. The spectrum of results in this battery of tests indicate that theobromine treatment results in the expression of genotoxic potential in some assays and the observed activity appears qualitatively and quantitatively similar to that of caffeine, a closely related methylxanthine.
在一系列体外试验中对可可碱（3,7 - 二甲基黄嘌呤）的遗传毒性活性进行了评估。在Ames试验中，无论有无S9激活，可可碱在最高浓度达5000微克/平板时均无致突变性。该化合物在CHO细胞中（无论有无S9激活）也未诱导出显著水平的染色体畸变，在Balb/c - 3T3细胞中也未诱导转化。在最大耐受浓度下，可可碱增加了小鼠淋巴瘤L5178Y细胞中TK - / - 突变体的频率。无论有无S9激活均观察到频率增加，且在2个独立实验中均可重复。在非激活试验条件下，人淋巴细胞和CHO细胞中获得了具有统计学意义的姐妹染色单体交换增加。这一系列试验的结果表明，可可碱处理在某些试验中导致了遗传毒性潜力的表达，并且观察到的活性在定性和定量上似乎与密切相关的甲基黄嘌呤咖啡因的活性相似。
