The role of the Peyer's patch in carcinogenesis. II. 3-Methylcholanthrene-induced lymphoid malignancies in rat Peyer's patches

Abstract

To determine whether B or T lymphoid malignancies could be induced following the exposure of lymphoid cells within different lymphoid organs to a potential chemical carcinogen, 3-methylcholanthrene (3-MC) was directly injected into surgically exposed Peyer's patches (PP), mesenteric lymph nodes (MLN), axillary lymph nodes (ALN) or spleens (SP) of Copenhagen rats. A high incidence of lymphoproliferative disorders was observed within rats which received 3-MC injections into the PP, but not in MLN, ALN or SP injected groups of rats. In addition to the PP environment, the dose of 3-MC and exposure to pristane were important factors in the induction of T versus B cell disorders. Whereas the B cell diseases were observed in pristane-treated rats which also received PP injections of low doses (5 or 50 micrograms) of 3-MC, in animals receiving a higher dose (500 micrograms) a much higher incidence of T cell disorders was detected. The observed lymphoproliferative diseases were categorized as B lymphocytic leukemias, B lymphomas or thymic lymphomas on the basis of histological examination of the tissues, white blood cell numbers and differentials, and the morphological and phenotypic characteristics of cell isolates. Abnormal DNA staining characteristics, increased soft agar cloning frequencies and metastasis of the leukemia or tumor cells indicated that malignant cells were associated with the proliferative diseases. Collectively the data indicate that primary lymphoid malignancies of either B or T cell origins may be preferentially and reproducibly induced by localizing low or high doses respectively, of 3-MC within the PP of rats exposed to pristane. These results suggest that PP may have a possible role in the carcinogenesis of lymphocytes following the exposure to chemical carcinogens via the gastrointestinal tract.

Changes in the DNA of lymphocytes from pristance treated rats

“…Thus, although pristane clearly induces a granulomatous substratum which appears to be a factor in the growth of hybridoma cells as ascites [2], there is also the possibility that ascites develop as a result of the effects of pristane on genomic activity. And second, pristane has a marked effect on the frequency and type of B lymphoid malignancies induced in 3-MC treated, Copenhagen rats [17]. In that the length of exposure to pristane pre-or post-3-MC treatment appears to be an important factor in the induction process (unpublished observation), we are currently examining the possibility that there is a correlation between the effects of pristane on the DNA of lymphoid cells and the susceptibility of the cells to the ultimate carcinogenic metabolites of 3-MC.…”

“…Furthermore, recent studies in our laboratory indicate that pristane facilitates the induction of lymphoid malignancies in rats. Specifically, whereas pristane or 3-methylcholanthrene (3-MC; a carcinogenic polycyclic aromatic hydrocarbon) treatments alone induced no malignancies or a low frequency of lymphoid malignancies, respectively, lymphoid leukemias and lymphomas were observed in > 40% of rats treated with both pristane and 3-MC [17]. The possible role of pristane in the aforementioned carcinogenic events may be attributable to one or more indirect effects; e.g., immunodepression [12], formation of a substratum for growth [2] and/or induction of presumed growth factors [3].…”

The tumor promoter pristane activates transcription by a cAMP dependent mechanism

“…Since pristane facilitates the development of 3-methylcholanthrene initiated malignancies in rats but does not have a carcinogenic effect alone, it can function as a tumor ]promoter [3]. Pristane can also induce plasmacytomas in BALB/c mice [4][5][6], enhance ascites formation in mice transplanted with hybridomas [5], and will induce viral plasmacytomas in mice [7].…”

Dietary effects of pristane on rat lymphoid tissues

“…Furthermore, studies in our laboratory indicate that pristane also affects the incidence of lymphoid malignancies induced by the potent car( gen 3-methylcholanthrene (3-MC 3) [13] and p~ erentially alters the propidium iodide staining characteristics of chromatin in lymphoid cells isolated from pristane treated rats and mice [14,15]. In light of the numerous biological effects attributed to pristane, it is of particular interest to note that appreciable amounts of pristane are present in common fruits and vegetables (manuscript submitted).…”