Glucocorticoid hormone effect on transplacental carcinogenesis and lung differentiation: influence of histocompatibility-2 complex.
In the mouse, the histocompatibility-2 (H-2) haplotype influences induction of lung and intestinal tumors by N-ethyl-N-nitrosourea (ENU) treatment of fetuses or infant mice. The differentiation of lung and intestinal epithelium is known to be regulated by glucocorticoids. We show that glucocorticoid-induced development of alveolar lung volume is H-2 influenced and that glucocorticoid treatment of fetuses also influences prenatal ENU induction of lung and intestinal tumors. These glucocorticoid effects on tumorigenesis are also H-2 influenced. The number of papillary lung tumors increased in B10 (H-2b) and decreased in B10.A (H-2a) mice. In the intestine, the number of tumors increased in H-2b females and decreased in H-2b males. In H-2a mice, the number of intestinal tumors was unchanged but their location was altered. We propose that the H-2 complex influences tumorigenesis in lung and small intestine by affecting the hormonal regulation of differentiation of target epithelial cells.
Oomen
L C
LC
Department of Molecular Genetics, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
van der Valk
M A
MA
Hart
A A
AA
Demant
P
P
D000231:Adenocarcinoma, Papillary / Q000139:chemically induced / Q000235:genetics; D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005038:Ethylnitrosourea; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000235:genetics*; D007421:Intestine, Small / Q000187:drug effects / Q000196:embryology*; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011663:Pulmonary Surfactants / Q000378:metabolism
D005938:Glucocorticoids; D006183:H-2 Antigens; D011663:Pulmonary Surfactants; D005038:Ethylnitrosourea