Induction of micronuclei by phenol in the mouse bone marrow: I. Association with chemically induced hypothermia.
Doses of xenobiotics at or near LD50 may result in substantial hypothermia in mice. Hypothermia has previously been associated with an increase in micronuclei (MN) formation. The present series of investigations examined the potential for phenol to induce hypothermia in mice and its correlation to previously reported MN induction. In order to examine the potential etiology of phenol-induced MN, evaluation of kinetochore status of MN was also carried out. Phenol-induced hypothermia was assessed in CD1 mice following a single ip dose of phenol ranging from 0-500 mg/kg. Phenol at 300 mg/kg or above caused significant and prolonged hypothermia in male and female mice (up to 7 degrees C decrease). In the micronucleus test, single ip doses of phenol to CD1 mice at 0, 30, 100, or 300 mg/kg produced a significant and prolonged hypothermia and a significant increase in MN only at 300 mg/kg; no marked effect on either body temperature or MN was observed at lower doses. A statistically significant increase in kinetochore-positive MN was observed at the 300-mg/kg dose; however, the response was considerably less than that observed for a known spindle poison. Hence, the induction of MN by phenol occurred only at a dose that produced substantial and prolonged physiologic hypothermia, but interruption of the cell spindle apparatus appeared to play only a minor role in MN formation. These data are suggestive of a threshold mechanism for the induction of MN by phenol treatment in mice.
Spencer
Pamela J
PJ
The Dow Chemical Company, Toxicology and Environmental Research and Consulting, Midland, Michigan 48674, USA. pjspencer@dow.com
Gollapudi
Bhaskar B
BB
Waechter
John M
JM
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007035:Hypothermia / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D018386:Kinetochores / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D019800:Phenol / Q000633:toxicity*
D009153:Mutagens; D019800:Phenol