Cytogenetic endpoints

Figure 2 Genetic and cytogenetic endpoints used in genetic ecotoxicology to assess individual-level effects in toxicant-exposed organisms. The large arrow indicates that severe or misrepaired damage to DNA or chromosomes may cause a cell to undergo apoptosis or programmed cell death.

THIERENS, H., et al., Inter-laboratory comparison of cytogenetic endpoints for the biomonitoring of radiological workers, Int. J. Radiat. Biol. 75 (1999) 23-34. 

Our cytogenetic endpoint of chromosomal damage shows a clear relationship between both urban or rural environments, and with the workplace location, where other outdoor factors might be excluded. Persons of the same profession, eg, officers from Budapest city-located offlce buildings and Budapest industrial worksite buildings show a 4-fold difference in the rate of aberrant cells. 

The demonstration of microsatellite instability and loss of heterozygosity in SMCs of human plaques suggests that genomic destabilization may play a pivotal role in atherosclerotic mechanisms. Furthermore, the use of accepted biomarkers of carcinogenic exposure-such as DNA adducts and cytogenetic endpoints recently has provided evidence consistent with the view that somatic cell alterations are critical in atherogenic process (reviewed in ref. 244). 

In vivo cytogenetic assay In vivo cytogenetic assay integrated into 28 d rodent toxicity study, provided it is adequate to support dinical trials and sampling within a day of last day of dosing In vivo cytogenetic assay and a 2nd in vivo endpoint, integrated wilh 28 d rodent assay and 1st in vivo endpoint if possible... 

Adopting the ideas proposed by Wurgler and Kramers (1992) and Kurelec (1993), it is proposed that the setting of water or sediment PNEC values for genotoxins should be based on sublethal biological endpoints expressed as statistically robust ECx or NOEC values. In practice, this could include the in vivo measurement of reproduction, development, growth, or specific cytogenetic macrolesions (namely, micronuclei, aneuploidy, and chromosomal aberrations) since these are known to relate to adverse phenotypic outcomes (Brusick 1987 Jha 2004). 

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