Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine-induced tumour formation in relation to H-2 haplotype.

Abstract

Male mice of the strain A/Sn, of its congeneic partner strain A.SW, C57BL/10ScSnA (abbreviated: B10), and of two congeneic strains on a B10 background (B10.A and B10.AKM) were investigated for their susceptibility to lung tumour induction by dimethylnitrosamine (DMN) administered either by intraperitoneal injection or in the drinking water. Strain B10 (haplotype H-2b) proved to be very resistant, whereas strains A/Sn (H-2a) and A.SW (H-2s) were highly susceptible. The introduction of the haplotypes H-2a and H-2m in the resistant strain B10 resulted in a significant increase in sensitivity towards DMN-induced lung tumour formation. Lung tumour incidences in male (B10.A x B10)F hybrids, receiving DMN in drinking water, were found to be intermediate between, and significantly different from, the incidences of identically-treated parent strains B10.A and B10. Males of back-cross (B10.A x B10) x B10 BC proved to be of low susceptibility to lung tumour formation by DMN, tumour incidence being very low and not significantly different from that observed in identically-treated B10 males. It is concluded that, at least in the model system of B10-derived congeneic strains, H-2 haplotype is one of the factors important in determining susceptibility towards DMN-induced lung tumours. Comparison of C3Hf (H-2k), C3H/Sn (H-2k) and the latter's congeneic strains C3H.B10 (H-2b) and C3H.NB (H-2p) of male mice showed that these strains were moderately susceptible to both lung tumour and hepatoma formation by DMN. Accordingly, the presence of an H-2 haplotype from a lung-tumour-resistant strain (H-2b, B10) on the background of a strain of intermediate susceptibility (C3H) does not decrease susceptibility to lung tumour formation. The results were considered in the light of the H-2 haplotype dependence of spontaneous lung tumours, and consequently attention has been paid to the histological types of the induced and spontaneous lung tumours.