Glucocorticoid Hormone Effect on Transplacental Carcinogenesis and Lung Differentiation: Influence of Histocompatibility-2 Complex

Abstract

In the mouse, the histocompatibility-2 (H-2) haplotype influences induction of lung and intestinal tumors byN-ethyl-N-nitrosourea (ENU) treatment of fetuses or infantmice. The differentiation of lung and intestinal epitheliumis known to be regulated by glucocorticoids. We show that glucocorticoid-induced development of alveolar lung volumeis H-2 influenced and that glucocorticoid treatment of fe-tuses also influences prenatal ENU induction of lung andintestinal tumors. These glucocorticoid effects on tumori-genesis are also H-2 influenced. The number of papillarylung tumors increased in BIO (H-2^b) and decreased in B10. A(H-2^a) mice. In the intestine, the number of tumors increasedin H-2b females and decreased in H-2^b males. In H-2^a mice, the number of intestinal tumors was unchanged but their location was altered. We propose that the H-2 complex influ-ences tumorigenesis in lung and small intestine by affecting the hormonal regulation of differentiation of target epithelialcells. [J Natl Cancer Inst 81:512-517, 1989]