| ABSTRACT: |
|
Ellagic acid (EA), derived from fruit ellagitannins, is known to be
antimutagenic and anticarcinogenic in various animal tumor models. In this
study, EA at a dose of 4 g/kg diet inhibited multiplicity of tumors
induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J
mice by 54%. This inhibition was dose related between 0.06 and 4.0 g/kg
diet. In contrast, two related compounds, esculin and esculetin, had no
effect on lung tumorigenesis. The biodistribution of EA was studied as a
function of dose and time after gavage of EA. The levels of EA in the lung
were directly proportional to the dose of EA between 0.2 and 2.0 mmol. The
maximum level of EA, corresponding to 21.3 nmol/g, was observed 30 minutes
after gavage with 2.0 mmol of EA/kg body wt, which corresponds to only 70
ppm of the administered dose. The levels in liver tissues were 10-fold
lower and reached a maximum 30 minutes after gavage. At this interval, the
blood level of EA was 1 nmol/ml. The inclusion of EA in cyclodextrin
doubles the level of EA in lung tissues. These results demonstrate that EA
localizes preferentially in lung tissues and confirm that EA administered
orally can inhibit lung tumorigenesis. |