Direct Damage to DNA

Formaldehyde may be genotoxic by a dual mechanism direct damage to DNA and inhibition of repair of mutagenic and carcinogenic DNA lesions by other chemical and physical carcinogens. 

Later 1-chlorooxirane (another metabolite of vinyl chloride) was found to be more reactive with DNA than chloroacetaldehyde [84]. Further study into the metabolism and reactivity of other alkyl halides revealed many of these molecules were either directly damaging to DNA or underwent metabolic transformation to reactive electrophiles capable of modifying DNA etheno DNA adducts were an abundant and important product of their reactivity. 

The term genotoxicity is a broader term and refers to potentially harmful effects on genetic material, which are not necessarily associated with mutagenicity. Thus, tests for genotoxicity include tests, which provide an indication of induced damage to DNA (but not direct evidence of mutation) via effects such as unscheduled DNA synthesis (UDS), sister chromatid exchange (SCE), DNA strand breaks, DNA adduct formation or mitotic recombination, as well as tests for mutagenicity. ... 

Genotoxicity refers to potentially harmful effects on genetic material (DNA), which may occur directly through the induction of permanent transmissible changes (mutations) in the amount or structure of the DNA within cells Such damage to DNA can occur at three levels. 

During irradiation, the holes produced in the ice phase are sequestered by the ice. This is not strictly true for the excess electrons some escape the ice phase and are selectively scavenged by DNA. The degree to which this increases the yield of electrons trapped by DNA is considered to be relatively small and therefore when computing yields of direct damage in DNA, the mass of the ice phase is usually excluded from the target mass. While ice is a relatively passive component of the system, it does provide an important reference point with respect to product yields. Electrons and holes are quite mobile in ice [87,88] it is a decent conductor. Consequently, even at low temperatures, the free radical yields are quite low, e.g., the yield of HO in ice at 77 K is 0.037 gmol/J [83]. This is just one example of a... 

Product analysis shows that the oxidative pathway of direct radiation damage to DNA results in a variety of products from each of the DNA bases [18] however, the dominant products are those from guanine such as 8-oxo-guanine and fapy-guanine as expected from the overall charge transport to guanine [18]. 

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