Comparison of basic fibroblast growth factor levels in clone A human colon cancer cells in vitro with levels in xenografted tumours.

We measured levels of basic fibroblast growth factor (FGF-2) in human colon cancer cells (clone A) in vitro and in xenografted solid tumours using a commercial enzyme-linked immunoassay. In Vitro, levels in unfed plateau phase or exponentially growing cells were low, averaging respectively about 2 and 8 pg 10(-6) cells. However, when solid tumours (average volumes 787 mm3) were cut into halves and either enzymatically disaggregated to obtain a cellular fraction or extracted in toto, levels were much higher. In the cellular fraction, values averaged 110 pg 10(-6) cells, while in whole tumour extracts, average values were 24 pg mg-1 tumour tissue. These results indicate that growth factor levels in solid neoplasms may differ markedly from those predicted from in vitro measurements. We hypothesise that the apparent increase in FGF-2 levels in vivo results primarily from the presence of a significant fraction of host cells (in particular, macrophages, which may contain high levels of FGF-2) within xenografted clone A neoplasms.

Acute toxicity in rats of chlorinated hydrocarbons given via the intratracheal route.

1. The approximate lethal dose (ALD) of six chlorinated hydrocarbons via the intratracheal route has been determined in rats and compared with published oral LD50 values. 2. The compounds tested in this study were dichloromethane, perchloroethylene, trichloroethylene, carbon tetrachloride, chloroform and ethylene dichloride. 3. A method of administering the materials intratracheally to unanaesthetized animals was developed. 4. The intratracheal ALD of the chlorinated hydrocarbons ranged from 3.1 to 17.5% of the oral LD50 and death was peracute. 5. Aspiration of chlorinated hydrocarbons may present more of a hazard than oral toxicity and should be considered when rendering first aid or emergency medical treatment.

Monochloroacetic acid exposure: a case report.

Monochloroacetic acid exposure causes significant burns but can also be lethal following exposures of less than ten percent of body surface area. There have been two known survivors of significant monochloroacetic acid exposure. This is a case report of one of those survivors. The mechanism of toxicity is unknown, and attempts to relate monochloroacetic acid toxicity is to that of monofluoroacetic acid have yielded inconsistent results. The best mode of therapy is unclear, and no antidote has been proven effective, although ethanol and glycerol monoacetate have been suggested. The details of this case may be helpful to those faced with similar situations and to those investigating the toxicology of monochloroacetic acid.

Pharmacokinetics of inhaled methyl chloride (CH3Cl) in male volunteers.

Six volunteers, 25-41 years of age, were exposed for 6 hr on separate days to 50 and 10 ppm of CH3Cl. Blood and expired air CH3Cl concentrations reached an apparent plateau during the first hour of the exposure and were proportional to the exposure concentration. Consistent with previous reports, the volunteers could be separated into two discrete groups based on the differences observed in their blood and expired air CH3Cl concentrations. Both groups eliminated CH3Cl rapidly once the exposure was terminated, but CH3Cl was eliminated more rapidly by those volunteers with the lower blood and expired air CH3Cl concentrations. The existence of these two groups can be explained by a twofold difference in the rate at which they metabolized CH3Cl; however, this difference is of questionable toxicological significance. Urinary excretion of the putative metabolite S-methyl cysteine was not related to the exposure; thus, it is not a valid means of monitoring occupational exposure to CH3Cl.

Kinetics and metabolism of inhaled methyl chloroform (1,1,1-trichloroethane) in male volunteers.

The kinetics of inhaled methyl chloroform (MC) and its principal metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA), were defined in six healthy male volunteers following single 6-hr exposures of 350 and 35 ppm. Blood and expired air MC concentrations were proportional to the exposure concentration and indicated that about 25% of the MC inhaled during the 6-hr exposure was absorbed. Elimination of MC was triexponential with half-lives estimated as 44 min, 5.7 hr, and 53 hr for the initial, intermediate, and terminal phases. Over 91% of the absorbed MC was excreted unchanged via the lungs, 5-6% was metabolized and excreted as TCE and TCA, and less than 1% remained in the body after 9 days. Urinary TCE and TCA excretion was extremely variable and indicated that urinary TCE and TCA measurements provide at best only a rough estimate of the exposure. These data suggest that the kinetics of MC in man are essentially first order at or below the current TLV of 350 ppm. Based on a comparison of the blood MC levels and amounts of MC metabolized, the rat is a better model than the mouse to predict the toxicity of MC in man.

Determination of phenol and pentachlorophenol in plasma and urine samples by gas liquid chromatography.

Gas chromatographic methods have been developed using a Supelco 1240-DA column for the determination of pentachlorophenol (PCP) in plasma and urine samples, and phenol in urine samples. These methods required no derivatization. Electron capture detection has been used for PCP determination, while flame ionization detection has been used to determine urinary phenol. The proposed phenol method avoids the use of perchloric acid, a safety hazard, as well as the formation of interfering compounds, which may be read as phenol if column resolution is inadequate.

Evaluation of rotenone and related compounds as antagonists of slow-reacting substance of anaphylaxis.

Rotenone (1), dihydrorotenone (2), isorotenone (3), mutarotenone (4), and deguelin (12) were found to be potent antagonists of slow-reacting substance of anaphylaxis (SRS-A) in vitro. However, these compounds were also shown to inhibit histamine, serotonin, and acetylcholine at only ten times their IC50 concentrations for SRS-A antagonism. Rotenone (1) and several related compounds were also evaluated in an in vivo guinea pig anaphylaxis model. Several of these compounds and FPL 55712 (I) were effective in prolonging collapse times of animals which received an aerosol challenge of an antigen to which they had been sensitized.

The effects of deuteration on the metabolism of halogenated anesthetics in the rat.

The authors studied the effects of substituting deuterium for hydrogen in several volatile anesthetics on their metabolism in the Fischer rat. Substitution of deuterium in the ethyl portion of methoxyflurane increased the metabolic production of fluoride ion by 19 per cent when administered at a concentration of 0.05 per cent. Total replacement of hydrogen by deuterium resulted in a 29 per cent decrease in the amount of fluoride produced, while deuteration of only the methoxyl group produced a 33 per cent decrease in fluoride produced. Deuteration of halothane resulted in a 15 or 26 per cent decrease in serum bromide at 0.75 per cent or 1.0 per cent, respectively. Deuteration in the ethyl portions of enflurane and two experimental agents, CF2HOCF2CFBrH and CF2HOCF2CCl2H resulted in 65, 76, and 29 per cent decreases in urinary fluoride, respectively. Anesthesia with deuterated chloroform at a concentration of 0.36 per cent produced a 35 per cent decrease in serum glutamic pyruvic transaminase (SGPT). It is concluded that deuteration of volatile anesthetics changes their metabolism, in most cases producing decreases in metabolism. This effect may lessen the organ toxicity believed to occur with some of these anesthetics.