Sleep time following anesthesia in mouse lines selected for resistance or susceptibility to fescue toxicosis.
In previous work, a mouse line selected for resistance (R) to fescue toxicosis had higher activities of two hepatic Phase II detoxification enzymes than a mouse line selected for fescue toxicosis susceptibility (S). The primary objective of the present study was to determine whether those same lines also differed in hepatic Phase I enzyme activity, estimated from sleep time (ST) following sodium pentobarbital anesthesia. Additional objectives were to determine whether ST differences between lines were modulated by endophyte-infected fescue in the diet (with or without an enzyme inducer) and whether ST of individual mice was correlated with the effect of a toxin-containing diet on the postweaning growth of those mice. In Exp. I, 24 males from each line were randomly assigned to each of five diets: control (commercial rodent food meal); E+ (50% endophyte-infected fescue seed, 50% control); E+P (the E+ diet supplemented with 1,000 ppm phenobarbital); E- (50% endophyte-free fescue seed, 50% control); and E-P (the E- diet supplemented with 1,000 ppm phenobarbital). After 4 wk on these diets, ST was measured on all the mice. A second ST was recorded on each mouse by randomly sampling one-fourth of the population after 1, 2, 3, or 4 wk on a pelleted rodent food diet. Regardless of diet, R mice had shorter first and second ST than S mice (P < 0.01), suggesting higher hepatic Phase I microsomal enzyme activity. Mice on both phenobarbital-supplemented diets had shorter first ST than mice whose diets did not include that microsomal enzyme inducer (P < 0.01). In Exp. II, ST was measured on male and female R and S mice (n = 280) after they had been fed the E- diet for 2 wk, then the E+ diet for 2 wk, and then a pelleted rodent food diet for 2 wk. Growth response to the E+ diet was the percentage of reduction in gain on the E+ diet compared to gain on the E- diet the previous 2 wk. As in Exp. I, S mice slept longer than R mice (P < 0.01). The residual correlation between ST and gain reduction associated with the E+ diet equaled 0.04. Thus, an animal's apparent Phase I enzyme activity did not predict its growth rate depression on the toxin-containing diet. Based on these and previous studies, divergent selection for toxicosis response in mice was successful partially by causing divergence in activities of hepatic Phase I and II detoxification enzymes.
Arthur
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Animal and Poultry Sciences Department, Virginia Polytechnic Institute and State University, Blacksburg 24061-0306, USA.
Kuehn
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Hohenboken
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WD
D000164:Acremonium; D000759:Adjuvants, Anesthesia / Q000493:pharmacokinetics*; D000821:Animal Feed / Q000009:adverse effects; D000818:Animals; D005260:Female; D005506:Food Contamination; D020022:Genetic Predisposition to Disease; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR / Q000235:genetics / Q000502:physiology*; D010424:Pentobarbital / Q000493:pharmacokinetics*; D010939:Plant Poisoning / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D006109:Poaceae / Q000382:microbiology*; D012641:Selection, Genetic; D013997:Time Factors
D000759:Adjuvants, Anesthesia; D010424:Pentobarbital