Synergistic effect of malathion and estrogen on mammary gland carcinogenesis

Breast cancer is the most frequent malignancy diagnosed in women and is a classical model of hormone-dependent malignancy. Over the past 15-20 years, epidemiological studies have pointed to an increased breast cancer risk associated with prolonged exposure to female hormones. On the other hand, environmental chemicals such as malathion, an organophosphorous pesticide used to control a wide range of sucking and chewing pests of field crops, may be involved in the etiology of breast cancers. Results indicated that estrogen alone increased average number of lobules per mm2 of rat mammary glands in comparison to control and malathion alone at 30, 124, 240 and 400 days after 5-day treatments. On the other hand, malathion alone significantly increased the number of ducts in stage of proliferation at 10-240 days after 5-day treatments. Furthermore, markers for cancer detection such as mutant p53, c-myc, c-fos and CYPs proteins were overexpressed after treatments. Atropine, an anticholinergic drug, counteracted these effects when it was combined with malathion under similar conditions. The combination of malathion and estrogen synergistically increased number of lobules and ducts per mm2 of rat mammary glands after treatments and inducing mammary cancer. It can be concluded that combination of an environmental substance such as the pesticide malathion and an endogenous substance such as estrogen can enhance the deleterious effects in human mammary glands inducing cancer and atropine is able to diminish these effects.