Effects of the pesticide chlorpyrifos on breast cancer disease. Implication of epigenetic mechanisms.

Chlorpyrifos (CPF) is an organophosphorus pesticide used for agricultural pest control all over the world. We have previously demonstrated that environmental concentrations of this pesticide alter mammary gland histological structure and hormonal balance in rats chronically exposed. In this work, we analyzed the effects of CPF on mammary tumors development. Our results demonstrated that CPF increases tumor incidence and reduces latency of NMU-induced mammary tumors. Although no changes were observed in tumor growth rate, we found a reduced steroid hormone receptor expression in the tumors of animals exposed to the pesticide. Moreover, we analyzed the role of epigenetic mechanisms in CPF effects. Our results indicated that CPF alters HDAC1 mRNA expression in mammary gland, although no changes were observed in DNA methylation. In summary, we demonstrate that the exposure to CPF promotes mammary tumors development with a reduced steroid receptors expression. It has also been found that CPF affects HDAC1 mRNA levels in mammary tissue pointing that CPF may act as a breast cancer risk factor.

Ethnic variation in the prevalence of AZF deletions in testicular cancer.

Seventy-six percent of testicular cancers of origin in Finns have been reported to exhibit AZF deletions. We analyze here 40 testicular tumor cases from Norway and Argentina and we found that AZF deletions occur also in non-Finnish cases but at significantly lower frequency (25%) than in Finland testicular tumor cases. This frequency difference can be attributed to the condition of genetic isolate of the Finnish population and the subsequent prevalence in this ethnic group of genetic factors involved in the origin of AZF deletions associated with malignancies. The finding of a correlation between AZF deletions and a given Y haplogroup would indicate the existence of Y lineages carrying AZF deletion-enhancing gene or genes. This possibility was explored using a set of Y-DNA-markers allowing the identification of Y lineages occurring at high frequency in Finns. We characterized the Y haplogroups in 32 normal Finn males (control group) and 17 cases of testicular cancer in Finns with and without AZF deletions. We found no association between Y lineages and AZF microdeletions, nor between AZF microdeletions and a Y microdeletion (DYS7C) exhibiting high prevalence (>50%) in Finns. The lack of correlation between AZF deletions and Y haplogroups indicates that the origin of these deletions is independent from the Y chromosome genetic background. No AZF deletions were found in familial cases of testicular tumors; hence, hereditary factors inducing the appearance of testicular malignancies in certain genealogies apparently do not increase the susceptibility to AZF deficiencies. AZF deletions are de novo events occurring in prezygotic or in post-zygotic stages. We propose that most AZF deletions associated with testicular tumors are due to post-zygotic Y microdeletions, while most cases of deletions associated with infertility are due to deletions occurring in the germ cell line of proband fathers.