Prenatal N-acetylcysteine prevents cigarette smoke-induced lung cancer in neonatal mice.
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.
Balansky
Roumen
R
National Center of Oncology, Sofia 1756, Bulgaria.
Ganchev
Gancho
G
Iltcheva
Marietta
M
Steele
Vernon E
VE
De Flora
Silvio
S
D000111:Acetylcysteine / Q000494:pharmacology*; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D008175:Lung Neoplasms / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012907:Smoking / Q000009:adverse effects*
D016166:Free Radical Scavengers; D000111:Acetylcysteine