Post-DNA Damage Mechanisms

Cellular processes that can protect DNA integrity once a DNA lesion has occurred are well-characterized. Broadly, these responses can be categorized as DNA repair, cell-cycle delay, apoptosis (i.e., programmed cell dealh), and cellular differentiation 

Based on the processes discussed above, cells have the ability to counteract a certain amount of chemical and environmental stress to maintain an overall level of organismal homeostasis and health. Thus, it is unlikely that any carcinogenic exposure, no matter how small, would always lead to an increased cancer risk (see Chapters 5 and 8). 

The extent to which hormetic information may be nsefnl in cancer risk assessment deserves consideration. At present, it is nnclear how hormetic dose-responses might influence the MOA information necessary for a departnre from the linearity assnmption. In practice, the hormetic relationships may provide a nsefnl backdrop for nnderstanding that carcinogenic thresholds can exist, bnt it still may not be 

Formaldehyde is another example of a mutagenic compound with evidence of nonlinearity. Based on limited evidence of respiratory cancer in humans and evidence of nasal tumors in rats and mice, ERA classifies formaldehyde as a probable human carcinogen. In rats, the most well-studied animal model for formaldehyde carcinogenesis, there is a threshold for tumor formation at 6 ppm. At levels below 6 ppm, formaldehyde induces DNA crosslinks in a dose-dependent manner wilh apparent low-dose linearity (Conolly et al. 2000 Slikko- et al. 2004). At doses above 6 ppm, concurrent with tumor formation, formaldehyde causes maiked cytotoxicity in the nasal passages of rats. 

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