Biomedical Engineering Reference
In-Depth Information
adducts, an additional measure of lipid peroxidation and free radical
damage, were detected in mice bone marrow and rabbit spleen but not in
primates in the same study (McCallum et al., 2011a, b). HNE, an end
product of lipid peroxidation like MDA may cause mutagenic adducts,
and possible effects on DNA (Halliwell and Gutteridge, 2007). Both
MDA and HNE have been reported to cause cancer. MDAwas found to
be carcinogenic to rats but not to mice in a NTP bioassay (NTP, 1988)
and HNE levels have been reported to increase in human breast cancer
(Kanhtala et al., 2011).
Unfortunately, no data exist on 8-oxodG or HNE-His adduct levels in
rats treated with methanol. There are several studies in rats, which
indicate that methanol can cause oxidative damage (TBA, MDA, and
enzymatic changes and effects on nonenzymatic antioxidants) in rats
following high methanol doses (Dobrzynska et al., 1999; Skrzydlewska
et al., 1998; Skrzydlewska and Farbiszewski, 1998, 1996). In mice,
rabbits, and primates, 8-oxodG or HNE-His adduct data is available but
no data on oxidative damage using indicators such as TBA, MDA,
enzymatic changes, and effects on nonenzymatic antioxidants end-
points are available. Direct comparison of rats and mice response to
oxidative damage as a result of methanol exposure is possible. On the
basis of similarity in metabolism, it may be assumed that the rat and
mouse are similar in their oxidative response to methanol. If this is the
case, one cannot rule out that oxidative damage may have played some
role in the rats carcinogenic study conducted by the Ramazzini Foun-
dation. In the Ramazzini Foundation lifetime oral methanol drinking
water study, the estimated top dose was between 1 and 2 g/kg (Soffritti
et al., 2002). In the Eppley drinking water study, methanol was used as a
control, the estimated top dose of methanol was
>
2000mg/kg (Apaja,
1980). In the NEDO inhalation study, the estimated top dose was about
600mg/kg based on blood methanol levels (NEDO, 1986, 1987).
Developmental effects are reported in rats and mice at a similar dose
possibly as a result of oxidative damage. Wells et al. (1997, 2005,
2009a, b) has suggested that ROS can effect embryonic development in
two ways. One effect maybe by altering signal transduction in the
embryonic cell; and the second possible way maybe by damage macro-
molecules, such as genes and proteins. In the developmental mouse
