Dose-Dependent Cytotoxicity of Chlorinated Hydrocarbons in Isolated Rat Hepatocytes

Dose-Dependent Cytotoxicity of Chlorinated Hydrocarbons in IsolatedRat Hepatocytes. DAHLSTROM-KJNG, L., COUTURE, J., LAMOUREUX,C, VAILLANCOURT, T., AND PLAA, G. L. (1990). Fundam. Appl. Toxicol.14, 833–841. The aim was to determine if isolated suspendedhepatocytes could differentiate between the effects of fourchlorinated hydrocarbons that are hepatotoxic In vivo and fourthat are not. Membrane integrity was assessed by measuring alanineaminotransferase (ALT) release after 30- to 180-min incubationsin vitro. From the results, the chlorinated hydrocarbons fellinto three groups: tetrachloroethylene and 1,1,2,2-tetrachloroeth-anewere the most potent cytotoxicants; CCl₄, 1,1,2-trichloroethane,and trichloroethylene exhibited intermediate cytotoxicity; andlow cytotoxicity was observed with CHCl₃, 1,1,1 -trichlo-roethane,and 1,1-dichloroethylene. Cytotoxicity ranking correlated poorlywith the reported In vivo hepatotoxicity of these agents. Theeffect of adding SKF-525A on the cytotoxicity of tetrachloroethyleneand CCI4 was also assessed. In addition, hepatocytes from ratspretreated with 2,5-hexanedione were used to determine if theywere more susceptible to the effects of CHCl₃, CCl₄ or tetrachloroethylene.SKF-525A decreased the cytotoxicity of both CO, and tetrachloroethylene,whereas pretreatment with 2,5-hexanedione enhanced their effect.The effects of both SKF-525A and 2,5-hexanedione on CCl in vitroare consistent with In vivo findings. However, tetrachloroethyleneis not hepatotoxic In vivo, suggesting that SKF-525A might actby stabilizing plasma membranes rendering the hepatocyte moreresistant to lysis. Overall, the results cast doubts on theuse of ALT release from isolated hepatocytes as an appropriatein vitro model for assessing hepatotoxic properties of chlorinatedhydrocarbons.     

Effectiveness of a Pregnancy Smoking Cessation Program

OBJECTIVE: To evaluate two nursing approaches to promoting smoking cessation during initial antenatal visits. DESIGN: Experimental, with assignment to interventions using a random, alternate-day strategy and blind assessment of smoking at baseline, 1 month postintervention, 36 weeks' gestation, and 6 weeks postpartum. SETTING/PARTICIPANTS: 224 daily smokers, fewer than 31 weeks gestation, during first prenatal visit, at a teaching hospital antenatal clinic. INTERVENTIONS: An evening class providing guidance on a self-help program for 2 hours on a group basis or 20 minutes on an individual basis during the prenatal appointment. MAIN OUTCOME MEASURE: Smoking cessation, confirmed by urinary cotinine levels. RESULTS: All women assigned to the referral intervention received a referral, but none attended the classes. In contrast, 93% assigned to the immediate intervention received the intervention. The group receiving immediate intervention had two to three times higher rates of cessation at all follow-up periods, with significant differences at the 1-month follow-up. There were certain similarities between the groups. CONCLUSION: Cessation interventions should be administered during the first prenatal visit.     

DECREASED EXPRESSION OF GALECTIN-3 IS ASSOCIATED WITH PROGRESSION OF HUMAN BREAST CANCER

Galectin-3, a member of the β-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of galectin-3 during the interactions between cells and laminin is not yet known, it has recently been observed that its expression is down-regulated at both the protein and the mRNA level in colon cancer tissues in correlation with progression of the disease. This study investigated the possibility that breast cancer cells might also exhibit decreased galectin-3 expression in association with their aggressiveness. The expression of galectin-3 was examined by immunoperoxidase staining, using a polyclonal antibody raised against recombinant galectin-3, in a collection of 98 human breast lesions including 12 fibroadenomas, 15 fibrocystic disease lesions, 22 in situ carcinomas, and 49 infiltrating ductal carcinomas, 19 of which had positive axillary lymph nodes. Normal breast tissue adjacent to the lesions was present in 59 biopsies. Normal breast tissue expressed high levels (3+) of galectin-3. High expression (2+ to 3+) was also found in most benign lesions examined. The expression of galectin-3 was significantly decreased in in situ carcinoma and this down-regulation was more pronounced in invasive ductal carcinoma, particularly when associated with infiltration of axillary lymph nodes. These data constitute the first observation that galectin-3 is down-regulated in breast cancer and suggest the decreased expression of this galactoside-binding lectin is associated with the acquisition of the invasive and metastatic phenotype.