Genetics of susceptibility to radiation-induced apoptosis in colon: two loci on chromosomes 9 and 16.
Apoptosis, a mechanism for removal of genetically damaged cells and for maintenance of desired size of cell populations, has been implicated in tumor development. Previously, we defined polymorphic loci for susceptibility to apoptosis of thymocytes Rapop1, Rapop2, and Rapop3 on mouse Chromosomes 16, 9, and 3, respectively, using recombinant congenic CcS/Dem strains, each of which contains a random set of 12.5% STS/A genome in the genetic background of BALB/cHeA. The STS/A alleles at these loci confer lower susceptibility to radiation-induced apoptosis of thymocytes than the BALB/cHeA. In the present study, we tested susceptibility of colon crypt cells to radiation-induced apoptosis. In contrast to apoptosis in thymus, the STS/A mice were more susceptible to apoptosis in colon than the BALB/cHeA. Among the CcS/Dem strains, CcS-4, CcS-7, and CcS-16 were more susceptible to apoptosis in colon than the BALB/cHeA; in thymus, the CcS-7 mice are less susceptible, and the CcS-4 and CcS-16 are not different from the BALB/cHeA. Thus, individual CcS/Dem strains showed different apoptosis susceptibility in the two organs. Analysis of (CcS-7 x BALB/cHeA)F2 hybrids revealed linkage of susceptibility to radiation-induced apoptosis of colon crypt cells to two loci on Chrs 9 and 16, to which Rapop2 and Rapop1 are mapped. The STS/A allele at the locus on chromosome 9 results in high susceptibility to apoptosis of colon crypt cells in mice homozygous for the BALB/cHeA allele at the locus on Chr 16. Although these two loci may be identical to Rapop1 and Rapop2, they affect apoptosis in colon in a way different from that in thymus.
Mori
N
N
Department of Applied Bioscience, Research Institute for Advanced Science and Technology, Osaka Prefecture University, 1-2 Gakuen-cho, Sakai, Osaka 599, Japan.
van Wezel
T
T
van der Valk
M
M
Yamate
J
J
Sakuma
S
S
Okumoto
M
M
Demant
P
P
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects*; D002874:Chromosome Mapping; D003106:Colon / Q000166:cytology / Q000528:radiation effects*; D003433:Crosses, Genetic; D005260:Female; D005720:Gamma Rays; D008040:Genetic Linkage; D006801:Humans; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000166:cytology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance / Q000235:genetics*; D013045:Species Specificity; D013950:Thymus Gland / Q000166:cytology / Q000528:radiation effects