Do Carcinogens Have a Threshold Dose? Pro and Contra
- 1.8k Downloads
With sound understanding of biological concepts, the notion of threshold effect levels has grown in acceptance especially for electrophile-induced mutations. However, mutagenesis is one part of the exposure-to-tumor process in chemical carcinogenesis. In the following chapter, we postulate diverse protective mechanisms that may contribute to no-effect thresholds in chemical carcinogenesis. Key mechanisms contributing to threshold doses are carcinogen detoxification and DNA repair. Elimination of cells harboring premutagenic DNA lesions by apoptosis and other cell death pathways and reduced proliferation rates within tissues may minimize mutation rates and therefore, contribute to threshold dose effects.
KeywordsNucleotide Excision Repair Base Excision Repair Threshold Dose MGMT Gene Genotoxic Carcinogen
- Coquerelle T, Dosch J, Kaina B (1995) Overexpression of N-methylpurine-DNA glycosylase in Chinese hamster ovary cells renders them more sensitive to the production of chromosomal aberrations by methylating agents – a case of imbalanced DNA repair. Mutat Res/DNA Repair 336(1):9–17CrossRefGoogle Scholar
- Kaina B, Fritz G, Coquerelle T (1993) Contribution O6-alkylguanine and N-alkyl-purines to the formation of sister chromatid exchanges, chromosomal aberrations and gene mutations: new insights gained from studies of genetically engineered mammalian cell lines. Environ Mol Mutagen 22:283–292PubMedCrossRefGoogle Scholar
- Seager AL, Shah UK, Mikhail JM, Nelson BC, Marquis BJ, Doak SH, Johnson GE, Griffiths SM, Carmichael PL, Scott SJ, Scott AD, Jenkins GJ (2012) Pro-oxidant induced DNA damage in human lymphoblastoid cells: homeostatic mechanisms of genotoxic tolerance. Toxicol Sci 128(2):387–397PubMedCentralPubMedCrossRefGoogle Scholar