Cell proliferation and tumor formation induced by eserine, an acetylcholinesterase inhibitor, in rat mammary gland.
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 17beta 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 17beta 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 17beta 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 17beta estradiol can be an initiator and promoter in this process.
Calaf
G M
GM
Center for Radiological Research, Columbia University Medical Center, New York, NY, USA. gmc24@columbia.edu
Parra
E
E
Garrido
F
F
D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004958:Estradiol / Q000633:toxicity; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D010830:Physostigmine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002800:Cholinesterase Inhibitors; D004958:Estradiol; D010830:Physostigmine