Pattern of N-Methyl-N-Nitrosourea (MNU) Induced Histotoxicity in Respiratory, Urinary and Reproductive Organs of Mice

Abstract

Animal models are important in the study of cancer pathogenesis. N-methyl-N-nitrosourea (MNU) is a potent human carcinogen. Tumor induction by a single intraperitoneal (i.p.) injection of MNU was studied in Swiss albino mice to determine the histo-toxic effects on selected organs of the respiratory, urinary and reproductive systems. Eighty mice, (40 males and 40 females) were randomly divided into four groups of 20 each. The test groups (twenty males and twenty females) were given i.p. injections of 50mg/kg of MNU, while the other two groups served as comparative control. They were monitored for seven months. One mouse from each of the 4 groups was sacrificed monthly over the exposure period. Selected organs (lungs, kidney and connective tissue around the mammary glands) were removed, fixed in 40% formal saline and processed using standard histological techniques. Mortality in the exposed animals was 1.25%. Organs of the exposed groups showed histopathological changes such as hyperplasia, infiltration of lymphocytes and collapsed alveolar sacs in the lungs; while vacuolation, vesicular and pleomorphic nucleation and increased nucleo-cytoplasmic ratio were observed in the kidneys. Lymphocyte infiltration was also observed in the glandular lumen of the connective tissues of the mammary gland, while organs of the control animals showed normal architecture. The degenerative changes observed are illustrative of the progression to cancer (carcinogenesis) that usually follows exposure to carcinogens in the environment. Interaction between the carcinogen and living cells resulted in damage to the organs of the exposed mice as evidenced by the distinct histopathological changes observed.