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Studies were conducted to assess the normal tissue-associated levels of pristane (2,6,10,14,-tetramethylpentadecane) in Copenhagen rats during ontogeny and adult life and to address whether or not dietary pristane can be adsorbed from the gut and disseminated throughout the body. During the course of this study the possible effects of dietary pristane on chromatin conformation of lymphoid cells were also examined by flow cytometry. The data indicated that 1) pristane crossed the placenta and accumulated in fetal tissues, 2) neonates were exposed to pristane via the colostrum, 3) there were significant increases in the amount of tissue-associated pristane in young adults and subsequent redistribution of the pristane to the muscle and adipose tissues in older rats and 4) after dietary exposure, significantly elevated levels of pristane were associated with the tissues and concomitant changes in chromatin conformation were observed. Collectively, these results suggest that pristane was adsorbed from dietary sources, disseminated to the tissues and exerted a transient, yet marked effect on chromatin of lymphoid cells in rats.

The dose response to 3-methylcholanthrene (3-MC), the promoter effects of 2,6,10,14-tetramethylpentadecane (pristane) and the target-organ specificity in the preferential induction of B-lymphoid malignancies versus thymic tumors were examined. Lymphoid malignancies were induced in approximately 30% of the Copenhagen rats treated with injections in Peyer's patches (PP) of low, intermediate or high doses of 3-MC. A low dose of 3-MC induced B-lymphocytic leukemias or B lymphomas, whereas thymic tumors were detected in rats treated with high doses. Co-treatment of rats with pristane and 3-MC resulted in increased incidences and decreased latency of the lymphoid malignancies observed, suggesting that pristane acts as a tumor promoter. To address the possible role of PP in the induction events, PP were surgically removed after 3-MC treatment and the remaining small intestine anastomosed. Thymic tumors, but no B-lymphoid malignancies, were observed, indicating that the PP environment was important in the induction of the B-lymphoid malignancies. Radiotracer studies also revealed that appreciable amounts of 3-MC were disseminated to the thymus within 24 hr after treatment of PP with a high dose of 3-MC. Furthermore, direct intrathymic injection of the thymus with 3-MC resulted in the development of thymic tumors only. These results support the hypothesis that the PP has an important role in early events in the carcinogenesis of B lymphocytes and in the dissemination of 3-MC to the thymus.

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