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Xenotropic virus expression and susceptibility to 3-methylcholanthrene-induced cancer
Abstract:
This paper reports the lack of genetic linkage between spontaneous production of substantial amounts of infectious xenotropic (X-tropic) virus and the susceptibility to chemically induced cancers in two inbred strains of mice, NZB/BLNJ and 129/J, and their genetic crosses. The parental strains and F1, backcross, and F2 progeny between these two strains were partially splenectomized to ascertain X-tropic viral status and were subsequently treated s.c. with 500 microgram of 3-methylcholanthrene in trioctanoin. Progeny from second backcrosses [(F1 X 129) X 129] were also tested for their X-tropic viral status and susceptibility to 3-methylcholanthrene carcinogenesis. Mice were observed for evidence of fibrosarcomas at the site of inoculation over a 10-month period. In this genetic system, spontaneous production of high titers of X-tropic virus segregated as a single autosomal dominant gene. Susceptibility to 3-methylcholanthrene-induced fibrosarcomas did not segregate in these crosses, and susceptibility did not correlate with the degree of X-tropic virus expression.
Insights
This study found no genetic link between xenotropic virus production and cancer susceptibility in mice. Cancer development was independent of virus expression in the tested mouse strains and their genetic crosses.
Area of Science:
- Virology
- Genetics
- Oncology
Background:
- Spontaneous xenotropic (X-tropic) virus production is observed in some mouse strains.
- Genetic factors influencing cancer susceptibility are complex.
- The relationship between endogenous retroviruses and chemical carcinogenesis is not fully understood.
Purpose of the Study:
- To investigate the genetic linkage between spontaneous xenotropic virus production and susceptibility to chemically induced cancers.
- To determine if X-tropic virus expression influences the development of fibrosarcomas induced by 3-methylcholanthrene.
Main Methods:
- Two inbred mouse strains (NZB/BLNJ and 129/J) and their genetic crosses were used.
- Mice underwent partial splenectomy to assess X-tropic viral status.
- Mice were subcutaneously inoculated with 3-methylcholanthrene to induce fibrosarcomas.
- Viral status and tumor development were monitored over 10 months.
Main Results:
- Spontaneous production of high titers of X-tropic virus segregated as a single autosomal dominant gene.
- Susceptibility to 3-methylcholanthrene-induced fibrosarcomas did not segregate in these crosses.
- No correlation was found between the degree of X-tropic virus expression and cancer susceptibility.
Conclusions:
- Genetic factors controlling X-tropic virus production are distinct from those controlling susceptibility to 3-methylcholanthrene-induced cancer.
- Spontaneous xenotropic virus expression does not appear to be a major determinant of chemically induced cancer in this mouse model.