Side effects of anastrozole in the experimental pre-menopausal mammary carcinogenesis.
The aim of this study was to assess side effects of aromatase inhibitor anastrozole in the prevention of N-methyl-N-nitrosourea - induced pre-menopausal mammary carcinogenesis in female Sprague-Dawley rats. This model mimicked situation in healthy, but from the point of view of the development of breast cancer, high-risk pre-menopausal women. <p align="justify">Aromatase inhibitor anastrozole was used as a chemopreventive agent taken by the animals in the food during the whole period of time of the experiment. Group 1 - the control group had taken food without anastrozole, the groups 2 and 3 with anastrozole in various concentrations - 0.05 mg/1 kg of food (ANA 0.05) and 0.5 mg/1 kg of food (ANA 0.5). </p><p align="justify">In anastrozole-treated animals in comparison with untreated animals, macroscopic changes of uterus and vagina were not found. The values of absolute and relative wet weight of uterus and vagina in the groups ANA 0.05 and ANA 0.5 were comparable with the control. Histological examination did not show atrophic changes in endometrium of uterus and in epithelium of vagina in anastrozole-treated animals. In the group ANA 0.5 myometrium was significantly grosser than in the group ANA 0.05 (P<0.05). Anastrozole neither affects parameters of plasma lipid metabolism (triacylglycerols, total cholesterol, low - density lipoprotein cholesterol and high - density lipoprotein cholesterol) nor serum levels of sex hormones (estradiol, testosterone, dehydroepiandrosterone). Compact bone thickness in the groups with anastrozole was significantly increased in comparison with untreated animals (P<0.001). A significant increase in body weight was found in the group ANA 0.5 compared with the control group (P<0.01). The significant increase in body weight gain was not attended by the significant increase in food intake.</p><p align="justify">The side effects of aromatase inhibitor anastrozole in the prevention of N-methyl-N-nitrosourea - induced pre-menopausal mammary carcinogenesis in female Sprague-Dawley rats on myometrium, compact bone thickness and body weight gain were observed. </p>


BACKGROUND
pre-menopausal mammary carcinogenesis, chemoprevention, aromatase inhibitors, anastrozole, side effects, female rats.
Sadlonova
V
V
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius Univeristy, Slovak Republic. vsadlonova@jfmed.uniba.sk
Kubatka
P
P
Kajo
K
K
Ostatnikova
D
D
Nosalova
G
G
Adamicova
K
K
Sadlonova
J
J
D000077384:Anastrozole; D000818:Animals; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008770:Methylnitrosourea; D009570:Nitriles / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000009:adverse effects*; D014599:Uterus / Q000473:pathology; D014621:Vagina / Q000473:pathology
D047072:Aromatase Inhibitors; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D008770:Methylnitrosourea