The present study aims at verifying the suitability of in vitro cell models as useful tools to profile the toxicological behaviour of environment-occurring endocrine active compounds (EACs), to discriminate among different mixtures, to define endpoints that can be easily employed to assess the risk associated to the exposure as well as used as markers for prevention studies. A modified protocol of BALB/c 3T3 cell transformation was used to predict the toxicity and carcinogenic potential of some environmental EAC mixtures and to discriminate their behaviour from that of Aroclors. The role of environmental PCBs in the multistep carcinogenesis and the mechanism of action was also investigated by the gap junction cell communication (GJIC) assay and by evaluating the ability to induce apoptosis. Because of the estrogenic activity of these compounds, we also used a panel of in vitro mammary models to assess endpoints related to the endocrine disrupting activity. Two cell lines, MCF-7 human breast cancer cells and HuMi-TTu-2, a non commercial tumorigenic cell line, were chosen as eligible targets. The cell proliferation assay and the soft-agar assay (clonogenic assay) were elected as the endpoints to test commercial Aroclors and two phytoestrogens, genistein and ferutinin, which are regarded as promising chemopreventive agents able to counteract the developing of hormonal-dependent cancers. The results gave evidence that the proposed endpoints were very sensitive to the action of the tested mixtures and compounds. We were able to evaluate the dose-related toxicity and transforming activity of environmental EACs, their role in the multistep carcinogenesis and their estrogen-like effects in target cells. We also could highlight different toxicological behavior in commercial and environmental EACs and evaluate dose-response relationships, that are perhaps the most controversial issue regarding EACs. By the means of in vitro assays, we also demonstrated that ferutinin show the same hormetic dose-effect relationship, as previously described for genistein.
IN VITRO ENDPOINTS TO PROFILE RISKS AND BENEFITS ASSOCIATED TO ENDOCRINE ACTIVE COMPOUNDS.
VACCARI, MONICA;SILINGARDI, PAOLA;GRILLI, SANDRO;CHIOZZOTTO, DANIELA;MASCOLO, MARIA GRAZIA;HORN, WOLFANGO;COLACCI, ANNAMARIA
2004
Abstract
The present study aims at verifying the suitability of in vitro cell models as useful tools to profile the toxicological behaviour of environment-occurring endocrine active compounds (EACs), to discriminate among different mixtures, to define endpoints that can be easily employed to assess the risk associated to the exposure as well as used as markers for prevention studies. A modified protocol of BALB/c 3T3 cell transformation was used to predict the toxicity and carcinogenic potential of some environmental EAC mixtures and to discriminate their behaviour from that of Aroclors. The role of environmental PCBs in the multistep carcinogenesis and the mechanism of action was also investigated by the gap junction cell communication (GJIC) assay and by evaluating the ability to induce apoptosis. Because of the estrogenic activity of these compounds, we also used a panel of in vitro mammary models to assess endpoints related to the endocrine disrupting activity. Two cell lines, MCF-7 human breast cancer cells and HuMi-TTu-2, a non commercial tumorigenic cell line, were chosen as eligible targets. The cell proliferation assay and the soft-agar assay (clonogenic assay) were elected as the endpoints to test commercial Aroclors and two phytoestrogens, genistein and ferutinin, which are regarded as promising chemopreventive agents able to counteract the developing of hormonal-dependent cancers. The results gave evidence that the proposed endpoints were very sensitive to the action of the tested mixtures and compounds. We were able to evaluate the dose-related toxicity and transforming activity of environmental EACs, their role in the multistep carcinogenesis and their estrogen-like effects in target cells. We also could highlight different toxicological behavior in commercial and environmental EACs and evaluate dose-response relationships, that are perhaps the most controversial issue regarding EACs. By the means of in vitro assays, we also demonstrated that ferutinin show the same hormetic dose-effect relationship, as previously described for genistein.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
