Cell proliferation and tumor formation induced by eserine, an acetylcholinesterase inhibitor, in rat mammary gland

Abstract

Abstract. Environmental chemicals may be involved in the etiology of breast cancer. There is substantial evidence that breast cancer risk is associated with prolonged exposure to female hormones. Among these hormonal influences a leading role is attributed to the ovarian hormone estradiol, since breast cancer does not develop in the absence of ovaries. The rat mammary gland has special characteristics that make it an ideal organ for studying development, cell proliferation and transformation. In vivo and in vitro model systems for cell proliferation and mammary carcinogenesis have allowed morphological and biochemical analysis under different experimental conditions. The aim of this study was to examine the effect of eserine, an acetylcholinesterase inhibitor, as are the organophosphorous compounds malathion and parathion, and 17ß estradiol on cell proliferation and tumor formation that takes place in the rat mammary gland after in vivo and in vitro treatment. These studies showed that eserine and 17ß estradiol were capable of inducing carcinogenesis in the epithelium of rat mammary glands. It was found that there was a significant increase in the number of cells per duct of the 44-day-old rat mammary gland after the 10-day eserine treatment, compared to the control. A higher increase was observed in the animals treated for 10 days with eserine followed by 30-daily injections of estrogen in comparison to control animals. In 12 animals, two mammary tumors were directly developed in response to 17ß estradiol injected at 39 days of age with a latency period of 180 and 245 days, respectively. Such tumors were metastatic to the lung. These results suggest that terminal end buds are major targets related to rat mammary carcinogenesis and 17ß estradiol can be an initiator and promoter in this process.

Acetylcholinesterase is associated with a decrease in cell proliferation of hepatocellular carcinoma cells

“…Some reports support a causal relationship between low AChE activity levels and enhanced cell proliferation and tumor formation, for instance the Calaf's group report showing that the inhibition of AChE by eserine was capable of promoting carcinogenesis in the rat mammary gland epithelium [40].…”

Malignant Transformation of Rat Kidney Induced by Environmental Substances and Estrogen

“…The dose of estrogen used in these experiments was lower than the previously reported one since malathion was used in combination in one of the groups and malathion alone induced mammary tumors under these conditions. In previous experiments [77] animals were treated with eserine twice a day for 10 days followed by 17β estradiol for 30 days (200 μg/100 g body weight) once a day, and in another one alone (300 μg/100 g body weight), twice a day for five days. …”

Catechol estrogens as biomarkers for mammary gland cancer

“…These data indicated that oxidant stress plays a crucial role in estrogen-induced carcinogenesis (40). Previous studies (41) have examined the effect of eserine, an acetylcholinesterase inhibitor, as are the organophosphorous compounds malathion and parathion, in the presence of 17β-estradiol on cell proliferation and tumor formation in rat mammary gland. These studies showed that eserine and 17β-estradiol induced carcinogenesis in the epithelium of rat mammary glands.…”