Effect of lung development on the histological pattern of lung tumors induced by ethylnitrosourea in the C3HeB/FeJ...

The number, size, and histological pattern of lung tumors collected 6 months after being induced in C3HeB/FeJ mice by ethylnitrosourea (ENU) treatment on one of days 13-19 of gestation, or days 5, 15, or 35 after birth, or as 9-month-old adults was investigated. The number of lung tumors induced increased when treatment occurred between days 13-16 and then decreased when treatment occurred on days 17-19 of gestation. There was a marked increase in lung tumor numbers induced on day 5 after birth, which decreased to much lower levels on days 15 and 35 after birth and in the treated adult mice. The size of lung tumors was greater in males than females in all groups and decreased as the age at the time of ENU treatment increased. A greater proportion (60-65%) of papillary tumors were induced following treatment on days 13-16 whereas, with one exception, alveolar lining tumors were the predominant histological type when treatment occurred after day 16. When treatment occurred on day 5 after birth, papillary tumors were once again the predominant type (66%) induced. The changes in tumor numbers induced and in the histological type of tumor induced occur at periods when major shifts in the histological development of the lung occur. The results indicate that the histological type of tumor induced by ENU treatment is developmentally regulated and suggests that alveolar lining and papillary tumors behave as two separate populations of tumors.