Influence of mouse major histocompatibility complex (H-2) on N-ethyl-N-nitrosourea-induced tumor formation in various organs.
The influence of the major histocompatibility complex (MHC) of the mouse (H-2) on carcinogen-induced tumorigenesis was investigated. Mice of five H-2 congenic strains on the C57BL/10 background were treated with the direct-acting carcinogen N-ethyl-N-nitrosourea at the age of 15 days, and examined for tumors when moribund. Significant differences between strains in susceptibility to N-ethyl-N-nitrosourea-induced tumors in lung, small intestine, and liver were found. For lung tumors the strains B10.A and 2R were most susceptible, the strains 4R and B10 were relatively resistant. The strain 5R was intermediate. Susceptibility to small intestine tumors was highest in the strain 2R, intermediate in the strain B10.A, the strains 4R, 5R, and B10 were relatively resistant. The location of the tumors in the intestine was also affected by H-2. In the strain 2R most tumors are located in the proximal part, in 4R in the distal part. Tumorigenesis in the liver was highest in the strain 2R, intermediate in the strains B10.A, 4R, and B10, and lowest in the strain 5R. We conclude that susceptibility to carcinogen-induced tumors in the lung, small intestine, and liver in congenic strains on the C57BL/10 background is H-2 haplotype dependent. Susceptibility to tumors in the lung and intestine has a similar strain distribution, but differs from that for liver tumors. Males were more susceptible than females in the strain B10 (lung tumors) and 4R (small intestine and liver tumors). This indicates haplotype- and organ-specific, sex-related influences on tumor development. The possible mechanism(s) of H-2 effects on chemically induced tumorigenesis are discussed. Apart from the well-known immunological functions of the MHC, the involvement of hormonally related effects of the MHC is considered as well.
Oomen
L C
LC
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
van der Valk
M A
MA
Hart
A A
AA
Demant
P
P
Emmelot
P
P
D000818:Animals; D005038:Ethylnitrosourea; D005260:Female; D006183:H-2 Antigens / Q000502:physiology*; D007414:Intestinal Neoplasms / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D012737:Sex Factors; D013045:Species Specificity
D006183:H-2 Antigens; D005038:Ethylnitrosourea