Serum levels of insulin-like growth factor-I in relation to organochlorine pesticides exposure.

CONTEXT: Insulin-like growth factor 1 (IGF-I) and organochlorine pesticides (OCs) have been involved in the pathogenesis of several diseases like cancer, diabetes and growth disorders. OBJECTIVE AND DESIGN: The potential relationship between the serum levels of various OCs and serum IGF-I was investigated in adults (176 men and 247 women) from a representative sample of the general population of the Canary Islands (Spain). RESULTS: After adjustment for potential confounders, which include body mass index, age, and IGF-binding protein-3 (IGFBP-3), IGF-I levels were significantly lower in the 247 women who showed detectable levels of p,p'-DDD (a DDT-metabolite) than in women who presented non-detectable levels of this pesticide (p=0.030), specially in 36-50 years old women. A similar negative relationship was also found between IGF-I and aldrin (a non-DDT-derivative) in women (p=0.049). In the group of 176 men, aldrin seemed to exert a similar negative effect on IGF-I (p=0.046) and this effect was clearly significant in the oldest group (51-65 years) (p=0.009). A non-linear dose-response curve was observed between Total Cyclodienes Body Burden (Total Cyclodienes; sum of aldrin, dieldrin and endrin) and IGF-I in men (p=0.024). These findings suggest that OCs could modulate the IGF-system in a way that is highly influenced by gender, age and by chemical or combination of chemicals implicated. Such circumstances may contribute to the development of a number of diseases related to IGF-I and should be taken into account in public health decisions.

Differential effects exerted on human mammary epithelial cells by environmentally relevant organochlorine pesticides either individually or in combination.

Organochlorine pesticides (OCs) have been associated with breast cancer development and progression. However, the deleterious mechanisms exerted by these contaminants are yet unclear and need to be further elucidated. In the present study, we investigated the effects of a number of OCs (previously detected in human serum from a Spanish population), individually or in combination, on normal human mammary epithelial cells (HMEC) at concentrations close to those found in human beings. The results obtained after a 96-h exposure indicated that OCs exert a clear cytotoxic effect on these cells at higher concentrations than those found in human beings. DDT-derivative organochlorines (DDT and its metabolites, DDE and DDD) are individually more cytotoxic than non-DDT-derivative organochlorines (aldrin and dieldrin). On the contrary, combinations of non-DDT organochlorines were clearly more cytotoxic than combinations of DDT-derivative organochlorines at concentrations close to those described in human serum. Additionally, transcriptional regulation arrays showed that the exposure of HMEC to an environmentally relevant mixture of OCs (p,p'-DDD plus p,p'-DDE plus o,p'-DDE plus aldrin plus dieldrin) sharply upregulated the expression of a number of protein kinases genes, such as ACVRL1, ALK-1, KIT, ERBB3, and ALK-1 at concentrations close to those detected in human populations. Taken together, these findings show a detrimental effect of OCs on human breast cells and indicate a possible association between exposure to organochlorine pesticide combinations and the induction of transformation processes in human breast cells.