Background: Although epidemiological studies indicate that ethanol consumption and the risk of breast cancer are positively associated in women, experimental animal models have not yet been developed that provide evidence to support this relationship. To clarify alcohol‐related liver injury, it is important to reproduce, in laboratory small animals, the liver fibrosis observed in human alcoholics. However, in mice the induction of fibrosis has failed. The present study describes the first experimental models to produce mammary tumors in female ICR mice and liver fibrosis in male ICR mice treated long‐term with ethanol.Methods: The study consisted of two parts. To induce mammary tumors, female ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 25 months, with solid diet supplied ad libitum. To induce liver fibrosis, male ICR mice were given 10% to 15% ethanol solution as the sole drinking fluid for 10 to 15 months. Control female and male mice were given tap water.Results: In 9 (45%) of 20 ethanol‐treated female mice, mammary tumors occurred at 8 to 24 months after ethanol intake began, whereas spontaneous mammary tumor was not found in the 20 control female mice. The tumors were composed histopathologically of either papillary adenocarcinoma or medullary adenocarcinoma of glandular epithelial origin. In the ethanol‐treated male mice, early hepatic fibrosis at the centrilobular and pericellular areas and central‐central bridging were observed at the 10th month, and marked fibrosis at the centrilobular, pericellular, and periportal areas and bridging between the neighboring vascular tissues were observed at the 15th month, which suggested that the initial fibrosis arose from the centrilobular area. No abnormalities other than mild fatty infiltration were found in livers of the control male mice.Conclusions: These murine models may be useful to study the role of ethanol in mammary tumorigenesis and the pathogenetic mechanisms of ethanol liver injury.

For high-performance liquid chromatography (HPLC) of thiamylal, one of the barbiturates, the drug in serum samples was extracted by two alternative liquid-liquid extraction techniques using hydrophilic acetonitrile as a solvent and subzero-temperature and salting-out methods. Acetonitrile was mixed with the sample, separated by cooling at -20 degrees C or addition of sodium chloride, and injected directly into the HPLC apparatus. In both the methods, thiamylal was extracted effectively in the acetonitrile phase and pH adjustment of the sample was not required. The salting-out extraction method is rapid and would be suitable for quantitation of drugs in many samples. To avoid coextraction of added salt, the subzero-temperature extraction method was applied to identification of thiamylal by gas chromatography/mass spectrometry and liquid chromatography-tandem mass spectrometry.

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