Selective activation of endogenous ecotropic retrovirus in hematopoietic tissues of B6C3F1 mice during the preleukemic phase of 1,3-butadiene exposure

Abstract

1,3-Butadiene (BD), a comonomer used in the production of synthetic rubber, is a rodent carcinogen. We have observed a marked increase in the incidence of thymic lymphoma in male B6C3F1 relative to NIH Swiss mice chronically exposed to BD in the absence of demonstrable differences in bone marrow (target organ) toxicity. Increased expression of murine leukemia virus (MuLV) antigens was also observed on lymphomas from BD-exposed B6C3F1 mice. Because NIH Swiss mice do not usually express endogenous retroviruses and their ecotropic proviral sequences are not intact, these fingings provide presumptive evidence of a role for endogenous retrovirus sequences in BD-induced lymphoma in the B6C3F1 mouse. The present study was conducted to examine the expression and behavior of endogenous retroviruses in these strains during the preleukemic phase of BD exposure. Chronic exposure to BD (1250 ppm) 6 hr/day, 5 days/wk for 3 to 21 weeks increased markedly the quantity of ecotropic retrovirus recoverable from bone marrow, thymus, and spleen of B6C3F1 mice. However, expression of other endogenous retroviruses (xenotropic, MCF-ERV) was not enhanced. No viruses of any type were found in similarly treated NIH Swiss mice. The mechanism of this increase in ecotropic retrovirus in B6C3F1 mice is believed to be de novo activation in greater numbers of cells because changes in the Fv-1 tropism of the replicating viruses or changes in Fv-1 host restriction were not found. Endogenous retroviruses are thus implicated in BD-induced leukemogenesis in B6C3F1 mice. Further studies will examine the role of retrovirus in BD-induced leukemogenesis and the mechanisms of activation of ecotropic proviral sequences in murine cells.