The effect of diethylstilbestrol as measured by host resistance and tumor susceptibility assays in mice

Abstract

As part of a program to develop and validate methodology to measure chemically induced immunotoxicity, the effect of DES on resistance of adult B6C3F1 female mice to various microorganisms and to challenge with syngeneic tumor cells was evaluated. The mice received sc injections of 50 microliter corn oil alone or of corn oil containing the equivalent of 0.2, 1, and 4 mg DES/kg X d for 14 d. Three days later they were challenged with Listeria monocytogenes, Streptococcus sp. influenza virus, herpes virus, Trichinella spiralis, or B16-F10 tumor cells. Host resistance parameters were mortality for the bacterial and viral systems, expulsion of adult parasites from the gut for T. spiralis, and lung weights for the B16-F10 tumor-cell model. Host resistance to L. monocytogenes, herpes virus, and T. spiralis was significantly decreased following DES exposure. Resistance to Streptococcus sp. was decreased, but not at a statistically significant level following these doses of DES. However a dose of DES at 8 mg/kg X d resulted in a highly significant decrease in resistance to the organism. Resistance to influenza virus was unaffected by the DES. In contrast to the above, host resistance to iv-administered B16-F10 tumor cells was significantly increased as a consequence of DES exposure. These model systems for measuring alterations in host resistance have been indicated to hold potential for the routine screening of drugs, chemicals, and environmental agents for their possible immune effects, both adverse and potentiating. The results indicate the importance of selecting the appropriate assay for evaluating a particular agent. They also stress the necessity for including host resistance assays along with assays to measure specific immune aspects, in order to assess in the intact animal the overall effect of complex immune interactions following exposure to a test agent.

Effects of Diethylstilbestrol and Estramustine Phosphate (Estracyt) on Natural Killer Cell Activity and Tumor Susceptibility in Male Mice

“…Recently it was reported that extension of the exposure time to DES to 2 weeks increased the host defense against B16-Fl0 cells after IV injection [37]. This cell line has been shown to be susceptible to macrophage-mediated cytotoxicity, and it was suggested that prolonged treatment with DES resulted in activation of cytotoxic macrophages.…”

Enkephalins and Endorphins

“…{Nicolet al, 1964). Rodents exposed to DES are also less susceptible to the formation of transplantable lung melanoma tumors (Fugmann et al ., 1983) as well as to certain plasmodial, babesial and trypanosomal infections {Cottrell et al, 1977;Kierszenbaum et al, 1974;Mankau, 1975).…”

“…The rapid clearance is due to hyperphagocytosis and increased division of Kupffers cells (Den Dulk et al, 1979;Kelly et al, 1962). The effects of , 1964, Fugmann et al, 1983Morahan et al ., 1984Cottrell et al, 1977Kierszenbaum et al, 1974Dean et al, 1980Pung et al, 1984Dean et al, 1980Luebke et al, 1984Dean et al, 1980Kalland and Forsberg, 1981Rank et al, 1982Toivanen, 1967Kittas and Henry, 1980Pung andLuster, 1984 Boorman et al, 1980;Dean et al, 1984 Loose andDiluzio, 1976;Nicolet al, 1964;Sljivic et al, 1975 Kalland andForsberg, 1978;Franks et al, 1975Waltman et al, 1971…”

Immune Function and Host Defense in Rodents Exposed to 60-Hz Magnetic Fields

“…monocytogenes infectious challenge. Host resistance to bacterial infection was assessed as previously described (Fugmann et al, 1983). On Exposure Day 24, mice received an iv injection in the lateral tail vein of 0.2 ml of a suspension of L. monocytogenes (serotype 4b; ATCC 13932) diluted in 0.85% saline to a dose calculated to produce an LD10-30 in the sham controls.…”

“…The mice continued to receive sham or magnetic field exposure through Exposure Day 28 and were monitored for death twice daily for 10 days after infectious challenge. Positive control animals received daily subcutaneous injections of 0.2 mg diethylstilbestrol (Sigma) per kilogram body weight for 14 days immediately prior to Listeria challenge (Fugmann et at., 1983).…”