Prostate exposition to chlordecone and molecular disruption related to tumor promotion. – CHLORPROST

Chlordecone (CLD) is an organochlorine insecticide that was used on the banana plantations of the French West Indies from 1973 to 1993. Because of its low dissipation in the environment, it has now caused long-term contamination of the environment, soil and water, and local agriculture and fisheries products. The West Indian population is continuously exposed to CLD, as shown by its presence in the blood of the entire population of these territories with likely consequences on health. The health issues are currently being evaluated.

An epidemiological study (Multigner, 2010) has shown a link between exposure to CLD and prostate cancer for a fraction of the Caribbean population of African origin, with the condition of having resided in mainland France. The risk is increased compared to the same type of sedentary population of the West Indies. However, banana plantation workers directly exposed to massive doses and with generally higher blood levels are not impacted more than the rest of the population. It appears from this study that chlordecone potentializes carcinogens and that exposure would be diet related, with the origin in mainland France. In addition, a preliminary study (F. Lawrence, 2012) carried out on rats showed that the prostate tissue is a major target, apart from liver tissue, for the distribution of CLD in the body. The objective of this project is to complement the existing pharmacological data by focusing our studies on chronic exposure to CLD; on the male genital tract, particularly the prostate gland, not studied so far, as it represents a major target of CLD and toxic action in the West Indies; evaluate the affinity of CLD for different tissues of this tract; determine the impact of this particular tissue exposure on the functioning of the prostate tissue.

Our project, in the beginning, will involve a toxicokinetic study to confirm our initial experimental results and evaluate the exposure parameters and retention of CLD in the prostate and due to the direct functional link existing in other tissues, of the male genital tract.
This study will be complemented by a MALDI mass spectrometry imaging of different tissues of the genital tract in animals exposed to CLD, to locate and quantify the CLD at a sub-tissue level. This point is related to the program ANR-11-CESA-0017 / HEPATOCHLOR that develops this technique on the liver. In a second step, this project will highlight the impact of CLD on the functioning of the prostate tissue. The CLD interacts with estrogen receptor a and ER ß. The expression of these varies, depending on the specific prostate tissue but also on the function of neoplastic development in these tissues. The link between the activity of endocrine disruption and the development of prostate cancer will be evaluated in vivo in this tumor model (TRAMP transgenic mouse) by determining the aberrant expression of genes related to prostate cancer (by transcriptomics) and the overall metabolic disturbance (by NMR profiling of metabolites) in this model "mouse", treated or not with the CLD at different stages of tumor development. A link will be established with the distribution and quantification of exposure to chlordecone in prostate tissue by statistical analysis aggregating all the data.
This project will highlight the determinants of retention of CLD in prostatic tissue and provide a better understanding of mechanisms of the predisposition development of prostate cancer induced by exposure to the CLD.