Mk. Selgrade et al., ENHANCED MORTALITY AND LIVER-DAMAGE IN VIRUS-INFECTED MICE EXPOSED TOP-XYLENE, Journal of toxicology and environmental health, 40(1), 1993, pp. 129-144
This study assessed effects of exposure to p-xylene, a ubiquitous air
pollutant, on mice infected with murine cytomegalovirus (MCMV), a mous
e model for a common human virus. It was postulated that adverse healt
h effects could occur as a result of (1) enhanced infection due to xyl
ene-induced immune suppression, (2) increased p-xylene toxicity due to
viral suppression of cytochrome P-450 (P-450), and/or (3) additive or
synergistic effects on liver function due to tissue injury by both p-
xylene and MCMV. Mice were exposed to filtered air, 600 or 1200 ppm p-
xylene 6 h/d for 4 d and infected with a sublethal dose of MCMV after
the first exposure. No deaths occurred among uninfected, p-xylene-expo
sed mice or infected, air-exposed mice; 34% and 0% mortality occurred
respectively in infected mice exposed to 1200 and 600 ppm p-xylene. Vi
rus titers in the liver and splenic natural killer cell activity were
unaffected by exposure to 1200 ppm p-xylene. Small but significant inc
reases in serum aspartate aminotransferase, alanine aminotransferase,
and lactate dehydrogenase activities, indicators of liver damage, were
observed at 4 d postinfection. p-Xylene exposure had no effect on the
se serum enzyme activities in uninfected mice, but 1200 ppm potentiate
d this effect in infected mice. MCMV significantly suppressed and p-xy
lene significantly increased total P-450 levels in the liver, but ther
e was no significant interaction between the two. Isozymes 1A1, 2B1/B2
, and 2E1 were decreased to a similar degree, suggesting that the viru
s does not target specific isozymes. Enhanced mortality was not due to
immune suppression. While p-xylene potentiated liver damage was cause
d by the virus, the magnitude of serum enzyme activities indicates tha
t this damage was not a likely cause of death. The cause of deaths is
unclear, results were consistent with the hypothesis that enhanced mor
tality was related to enhanced xylene toxicity due to suppression of P
-450, although additive or synergistic damage to tissues other than li
ver cannot be ruled out.