Carcinogenesis Advance Access published online on May 20, 2009
Carcinogenesis, doi:10.1093/carcin/bgp128
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Prenatal N-acetylcysteine prevents cigarette smoke-induced lung cancer in neonatal mice
1 National Center of Oncology, Sofia 1756, Bulgaria
2 Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy
3 National Cancer Institute, Rockville, MD 20892, USA
* To whom correspondence should be addressed. Tel: 39-010-353.8500; Fax: 39-010-353.8504; E-mail: sdf{at}unige.it.
Certain adult diseases may have their origin early in life, and perinatal exposures may contribute to cancers both during childhood and later in life. We recently demonstrated that mainstream cigarette smoke (MCS) induces a potent carcinogenic response in mice when exposure starts soon after birth. We also showed that the antioxidant N-acetylcysteine (NAC) prevents the extensive nucleotide and gene expression alterations that occur "physiologically" at birth in mouse lung. The present study was designed to evaluate whether administration of NAC during pregnancy may affect the yield of tumors in mice exposed to MCS, starting after birth and continuing for 120 days. The results obtained showed that, 210 days after birth, one adenoma only was detectable in sham-exposed mice. In contrast, as much as the 61.1% (33/54) of MCS-exposed mice born from untreated dams had lung tumors, including both benign tumors and bronchoalveolar carcinomas. Treatment with NAC during pregnancy strikingly inhibited the formation of benign lung tumors and totally prevented occurrence of carcinomas. In addition, prenatal NAC inhibited the MCS-induced hyperplasia of the urinary bladder epithelium. These findings demonstrate for the first time that treatment during pregnancy with an antioxidant chemopreventive agent can affect the induction of tumors consequent to exposure to a carcinogen after birth.
Received March 17, 2009; revised April 16, 2009; accepted May 15, 2009.