Prepubertal Zearalenone Exposure Suppresses N-Methyl-N-nitrosourea-Induced Mammary Tumorigenesis but Causes Severe Endocrine Disruption in Female Sprague-Dawley Rats

Abstract

The effect of prepubertal exposure to zearalenone, an estrogenic mycotoxin, on N-methyl-N-nitrosourea (MNU)-induced mammary tumorigenesis and its influence on reproductive organs were examined in female Sprague-Dawley rats. Prepubertal rats were treated daily with either 0.1 or 10 mg/kg body weight of zearalenone between 15 and 19 days of age and compared with zearalenone-untreated animals (30 rats in each group). Six rats in each group were autopsied at 28 days of age, and their growth was evaluated. All remaining rats were given 50 mg/kg body weight MNU at 28 days of age and followed by monitoring for occurrence of mammary tumors ≥1 cm in diameter. Zearalenone did not affect body weight increase, and mammary glands showed similar development at 28 days of age (time at carcinogen administration). Both low- and high-dose zearalenone treatment significantly reduced incidence of mammary tumors ≥1 cm in diameter but did not influence latency (time between MNU administration and harvest of mammary tumor ≥1 cm in diameter) compared with untreated controls. Zearalenone dose dependently suppressed the number of histologically detected tumors (carcinomas) and multiplicity; the suppression was significant with high-dose treatment. However, high-dose treatment caused significantly earlier vaginal opening, both low- and high-dose treatment significantly caused irregularity of estrous cycle (persistent estrus or prolonged diestrus) at 8 to 10 wk of age, and zearalenone dose dependently increased the number of anovulatory rats (ovaries without newly formed corpora lutea) at 37 wk of age. Thus, short-duration zearalenone treatment in the prepubertal period suppressed subsequent mammary cancer occurrence but also severely damaged ovarian functions. This suggests that ingestion of foods containing zearalenone in the infantile period can have dramatic effects in later life.