Cytotoxicity sublethal

Table 14.3 Characteristics of an effective cell model for screening for sublethal cytotoxicity [4, 11, 33, 36].

O Brien, P.J. (2008) Chapter 13 High content analysis of sublethal cytotoxicity in human HepG2 hepatocytes for assessing potential and mechanism for chemical and drug-induced human toxicity, in High Content Screening Science, Techniques and Applications (ed. S.A. Haney), John Wiley Sons, Hoboken, NJ,... 

Some drugs that exert their maximum cytotoxicity during the S-phase of the cycle also prevent cells from progressing through the cell cycle to the S-phase this is accomplished by sublethal inhibition of RNA and protein synthesis. The antimetabolites methotrexate, fluo-rouracU, and mercaptopurine all can inhibit RNA synthesis in Gi- and Gz-phases and inhibit DNA synthesis during S-phase. This inhibition of cell cycle progression actually may result in reduced cytotoxicity, and such agents have been termed S-phase-specific but self-limited. 

The recovery period after drug exposure is important for many reasons. This period permits the re-establishment of metabolic equilibrium when inhibition is used as a pharmaceutical test. In addition, cells can recover from sublethal damage or indicate effects of late cytotoxicity, which are not revealed in alternative tests. 

The presence of mercury in fish, thermometers, dental amalgams, vaccine preservatives, and the atmosphere has increased public health concerns about adverse health effects in humans exposed to relatively low levels of mercury. The lack of a clear correlation between mechanistic research on mercury toxicity and sublethal non-cytotoxic effects and lack of consideration of mercury-induced immunotoxicily as an important health outcome have limited the application of science-based risk assessment on this issue (Silbergeld Devine, 2000). 

Sublethal Doses of APAP Sensitize Hepatocytes to the Cytotoxic Effects... 

Garnett CT et al. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res 2004 64 7985-7994. 

Zahn, T. Braunbeck, T. Cytotoxic effects of sublethal concentrations of malachite green in isolated hepatocjrtes from rainbow trout (Oncorhynchus mykiss). Toxicol. In Vitro 1995, 9, 729-741. 

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