BRACKEN FERN CARCINOGENESIS - MULTIPLE INTRAVENOUS DOSES OF ACTIVATEDPTAQUILOSIDE INDUCE DNA-ADDUCTS, MONOCYTOSIS, INCREASED TNF-ALPHA LEVELS, AND MAMMARY-GLAND CARCINOMA IN RATS

Aims: (1) establish a rat model for investigating ptaquiloside (PT) ca rcinogenesis via intravenous dosing; (2) determine the role of activat ed PT (APT) in this model; and (3) monitor changes at molecular (DNA a dducts, TNF alpha levels) and cellular (histopathology) levels. Method s: Sprague-Dawley rats were dosed with PT or APT intravenously for 10 consecutive weeks. One group of animals was sacrificed immediately for TNF alpha and DNA adduct analyses. A second group of animals was kept alive for 30 more weeks to allow for tumour formation. Tissues were c ollected at the end of the experiment for histopathological studies. R esults: Rats dosed with PT or APT showed marked increase in monocyte a nd TNF alpha levels. These levels remained high even 30 weeks after th e last dosing. Analysis of DNA showed the presence of DNA adducts in A PT-treated animals in target organs. In addition, 40% of APT-treated r ats developed mammary gland carcinomas. Conclusion: This is the first study to demonstrate the potential of activated PT as a carcinogen in vivo. In addition, our findings suggest that PT exposure can be monito red using monocyte and TNF alpha levels. (C) 1998 Academic Press.