The present study provides systematic evidence indicating a direct relationship between environmental temperature, rectal temperature and ethanol lethality. Male, C57 BL/6J mice, previously housed at room temperature (23 +/- 1 degree C), were injected intraperitoneally with 4.8 to 9.2 g kg-1 ethanol and then exposed for 24 h to ambient temperatures that did not appreciably exceed the thermally neutral range for sober mice (20 to 35 degrees C). There was a direct relationship between temperature and ethanol lethality at 8 and 24 h after injection. The 8 h LD50 increased by 64%, from 5.3 to 8.7 g kg-1, as environmental temperature decreased from 35 to 20 degrees C. The 24 h LD50 increased by 51%, from 5.3 to 8.0 g kg-1, across this temperature range. Each 5 degrees C reduction in ambient temperature induced a significant decrease in the rectal temperature of ethanol-injected mice. Mean rectal temperature ranged from 2.2 degrees C above baseline at an ambient temperature of 35 to 15 degrees C below baseline in the 20 degrees C environment. Ethanol induced a significant dose-related hypothermia in mice exposed to the 20, 25 and 30 degrees C environments but did not produce hypothermia in animals kept in the 35 degrees C environment. These findings indicate that the potency of potentially lethal ethanol doses varies with body temperature in accordance with partition and membrane expansion-fluidization theories of anaesthesia.
Rates of hydroxylation of benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), chrysene, acetanilide (AC), 7,12-dimethylbenz[a]anthracene (DMBA), and 17β-estradiol (E2) in vitro could be increased by as much as 70-fold by additions of micromolar quantities of hematin. Such increases were observed primarily when extrahepatic tissues were utilized as the enzyme source; the greatest increases occurred with rabbit brain. Mixed-function oxygenations of aniline, ethylmorphine, benzphetamine, N-2-fluorenylacetamide (FAA), dibenz[a, h] anthracene(DBA), and benz[a] anthracene (BA), were affected minimally or not at all by hematin additions. Analyses of metabolites of BaP, AC and DMBA with high-pressure liquid chromatography revealed a high degree of position specificity for the hematinmediated reactions. This specificity was dependent upon the enzyme source, e.g. with rabbit kidney as enzyme source and AC as substrate, hematin additions resulted in only minor increases (30–40 per cent) in quantities of 3- and 4-hydroxylated metabolites and decreases (approximately 40–50 per cent; possibly a result of further degradation) in amounts of 2-hydroxylated AC. With hematin additions to rabbit brain homogenates, quantities of the measured 2-hydroxylated AC increased by 10 to 12-fold and of the 3-hydroxylated product by 3 to 4-fold, but no detectable changes in 4-hydroxylated AC were observed. With BaP as substrate, hematin elicited the formation of large quantities of an unidentified and hitherto undetected metabolite. Results of the study were consistent with the concept that hematin additions result in the reconstitution of a number of functionally distinct, tissue-specific cytochrome P-450 apoproteins.
