1. Br J Cancer. 1999 May;80(5-6):855-61.
Propylnitrosourea-induced T-lymphomas in LEXF RI strains of rats: genetic
analysis.
Lu LM(1), Shisa H, Tanuma J, Hiai H.
Author information:
(1)Department of Pathology and Biology of Disease, Graduate School of Medicine,
Kyoto University, Japan.
Oral administration of propylnitrosourea (PNU) in drinking water induces high
incidence of lympho-haemopoietic malignancies in rats. Previously we reported
that F344 strain rats were highly susceptible to T-lymphomas, and LE/Stm rats, to
erythro- or myeloid leukaemias. For analysis of the genetic factors determining
types of diseases, we have established LEXF recombinant inbred strains of rats
comprising 23 substrains, each derived from intercross between F344 and LE/Stm
rats. Rats of 23 LEXF substrains were given PNU, and the development of tumours
was observed. The overall incidence of haemopoietic tumours ranged from 100% to
66.7%, and the fractions of T-lymphomas, from 100% to 4%, showing a continuous
spectrum. Based on the genetic profile published as a strain distribution pattern
table for the LEXF, we screened the potential quantitative trait loci involved in
determination of the types of disease and length of the latency period.
Statistical calculation was performed using the Map Manager QT software developed
by Manly. Four loci, on chromosome 4, 7, 10 and 18, were suggested to associate
with the T-lymphoma susceptibility and three loci, on chromosome 1, 5 and 16,
with the length of the latency period. These putative loci were further examined
in backcross (F344 x LE)F1 x LE. Among seven loci suggested by the recombinant
inbred study, three loci, on chromosome 5, 7 and 10, were significantly
associated with T-lymphomas and another locus on chromosome 1, just weakly. These
observations indicate that PNU-induced lymphomagenesis is a multifactorial
genetic process involving a number of loci linked with susceptibility and
resistance.
PMCID: PMC2362294
PMID: 10360666 [PubMed - indexed for MEDLINE]
PUBMED: 10360666
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