Multiple genes in the H-2 complex affect differently the number and growth rate of transplacentally induced lung...

Although several studies have demonstrated that the H-2 haplotypes influence susceptibility to both spontaneous and carcinogen induced lung tumours in mice, little is known about the nature of their action. In this study, we analysed the effects of four haplotypes (a, h2, h4, b) with a C57BL/10ScSn background on the histological type of the tumours, their incidence, numbers and size. The tumours were studied in 8 and 16 week old progenies of mothers which were injected on the 15th day of pregnancy with N-ethyl-N-nitrosourea. Even with the limited number of haplotypes tested, our data show that the effect of H-2 genotype is both genetically and biologically complex. Lung tumours of the alveolar type were detected in appreciable numbers only in a and h2 mice, indicating that their incidence is controlled by gene(s) to the left of I-E. On the other hand, tumours of the papillary type were present in all streams in approximately the same numbers, but their size differed between strains, being largest in a mice, intermediate in h2 and h4 mice, and smallest in b mice. Moreover, in contrast to a, h2 and h4 mice, in b mice the average tumour size did not increase in the time interval between the age of 8 and 16 weeks. Apparently, several MHC genetic factors are responsible for the control of growth and incidence of the transplacentally induced lung tumours. At least one factor maps to the left of I-E, other(s) to the right of S. It is possible that these genes act through different mechanisms, since they affect the numbers of alveolar tumours, but with papillary tumours their main effect is on their size (growth intensity).