Labeling index

LG j8-Lact< obulin LGL Large granular lymphocyte LH Luteinizing hormone LHRH Luteinizing hormonereleasing hormone LI Labelling index LIS Lateral intercellular spaces LMP Low molecular mass polypeptide... 

GPT = glutamic pyruvic transaminase GSH = glutathione Hemato = hematological hr = hour(s) LCso= lethal concentration. 50% kill LOAEL = lowest-observed-adverse-effect level LI = labeling index M = male min = mlnute(s) mo = moth(s) musc/skel = musculoskeletal NOAEL = no-observed-adverse-effect level NS = not specified Resp = respiratory ... 

Experimental design The authors investigated the ability of chloroform vapors to produce toxicity and regenerative cell proliferation in female B6C3Fj mice and male Fischer 344 rats. Groups of 5 animals were exposed to 0, 1,3, 10, 30, 100, or 300 ppm chloroform via inhalation for 6 hours a day for 7 consecutive days. Actual exposure concentrations measured for mice were 0, 1.2, 3.0, 10.0, 29.5, 101, and 288 ppm and for rats were 0, 1.5, 3.1, 10.4, 29.3, 100, and 271 ppm. Necropsies were performed on day 8. Animals were administered bromodeoxyuridine (BrdU) via implanted osmotic pump for the last 3.5 days. Cell proliferation was quantitated as the percentage of cells in S-phase (labeling index = LI) measured by the immunohistochemical detection of BrdU-labeled nuclei. 

P-450 content was induced in mice given 600 but not 300 mg/kg 1,4-dichlorobenzene for treatments of 4 and 13 weeks. Microsomal 7-pentoxyresorufm 0-depentylase activity was significantly induced in mouse liver microsomes at doses of 300 and 600 mg/kg 1,4-dichlorobenzene. Western immunoblotting studies demonstrated that 1,4-dichlorobenzene induced CYP2B isoenzyme(s) in mouse liver microsomes at 300 and 600 mg/kg 1,4-dichlorobenzene. Hepatocyte labeling index values were significantly increased in mice given 300 and 600 mg/kg 1,4-dichlorobenzene for 4 weeks (420% and 395% of controls, respectively) (Lake et al. 1997). 

The BrdU hepatocyte labeling index values in male F344 rats given 25, 75, 150, and 300 mg/kg/day... 

In short-term renal toxicity studies in rats gavage administration of 1,1,2,2-tetra-chloroethane caused renal toxicity as evidenced by an increased renal tubule cell labeling index, indicating replicative DNA synthesis. In 2-year studies 1,1,2,2-tetrachloroethane administered by gavage produced an increased incidence of hepatocellular carcinomas in mice but not in rats. In one epidemiological study of exposed army workers there was a slight increase in deaths due to genital cancer and leukemia. Exposure levels were not available,... 

The mitotic index is the fraction or percentage of cells in mitosis within a given cell population. The thymidine labeling index is the fraction of cells incorporating radioactive thymidine. They represent cells in M-phase and S-phase and define the proliferative characteristics of normal and tumor cells. 

Administration of catechol (1.5% in the diet) for 20 weeks induced mild to moderate hyperplasia but no papillomatous lesions in the forestomach in Syrian hamsters. Labelling index, after an intraperitoneal dose of [ HJthymidine, was elevated in the pyloric region, but not in the forestomach or urinary bladder (Hirose et al., 1986). 

Administration of hydroquinone (0.5% in the diet) for 20 weeks did not induce hyperplasia or papillomatous lesions in the forestomach in Syrian golden hamsters (Hirose etal., 1986). In male Fischer 344 rats, oral administration of hydroquinone for eight weeks (0.8% in the diet) did not induce hyperplasia or DNA synthesis, as measured by BrdU-labelling index in the forestomach epithelium. No cell proliferation, increased DNA synthesis or increase in pepsinogen-isoenzyme-1-altered neoplastic foci was observed in the pyloric mucosa (Shibata et al., 1990). 

Extensive destruction of the olfactory epithelium was observed in male Fischer 344 rats exposed to 200 ppm [780 mg/m ] methyl bromide for 6 h per day for five days. By day 3, despite continued exposure, there was replacement of the olfactory epithelium by a squamous-cell layer, followed by progressive reorganization toward the normal architecture, and by week 10,75-80% of the epithelium appeared histologically normal. Olfactory epithelial-cell replication was maximal on day 3 of exposure, with a labelling index of 14.7% compared with 0.7% in the controls (Hurtt et al., 1988). Degeneration and subsequent regeneration were also observed in an inhalation experiment w ith Fischer 344 rats exposed to 175 ppm [680 mg/m ] 6 h twice, separated by a 28-day interval (Bolon et al., 1991). 

For in vivo incorporation of BrdU in experimental animals, inject 10-100 mg/kg of BrdU in 0.9% saline by the ip route. A concentration of 10 mg/mL is routinely used. The animal is sacrificed after 1 h for labeling index studies or at 1-2 hourly time intervals for cell cycle progression studies In vivo incorporation of BrdU into humans at Mount Vernon Hospital involves iv injection of 200 mg of BrdU in 20 mL of normal saline as a single bolus over 3-5 min... 

In human tumors, both the labeling index (LI) and Ts can be calculated from a single observation (5). These two parameters can be used to calculate the potential doubling time (rpo,), which describes the shortest possible time a cell... 

Wilson, G D, McNally, N. J, Dunphy, E, Karcher, H., and Pfragner, R (1985) The labelling index of human and mouse tumours assessed by bromo-deoxyuridine staining in vitro and in vivo and flow cytometry Cytometry 6, 641-647. 

However, be aware that in spite of the usefulness of the MIB-1 antibody in assessing the rate of cell proliferation, the classification of cancers (e.g., breast cancer) by the size of the primary tumor and the presence and extent of lymph node metastases does not adequately explain differences in the clinical outcome of individual patients. Cell proliferation indices are commonly used, along with other diagnostic parameters, to estimate the risk of recurrence of a cancer for individual patients. Therefore, it is important to understand the relationship between various indices of proliferation such as MIB-1 labeling index and detection by either in situ hybridization or polymerase chain reaction. This approach will lead to quality assurance in diagnosis. 

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