Biomedical Engineering Reference
In-Depth Information
FIGURE 7.18 Biochemical pathways for endogenous and xenobiotic-
enhanced formation and detoxification of reactive oxygen species (ROS), and
repair of oxidatively damaged cellular macromolecules. ROS include superoxide
(O
2
), hydrogen peroxide (H
2
O
2
), and hydroxyl radicals (HO
). Teratogenesis
is postulated to result from embryonic macromolecular damage and/or ROS-
mediated alterations in embryonic signal transduction. If embryonic ROS
formation exceeds the proximal capacity for ROS detoxification and/or repair
of cellular macromolecules, this imbalance can result in enhanced teratogenesis,
even at a therapeutic drug concentration or generally “safe” exposure level for an
environmental chemical. Abbreviations: ATM, ataxia telangiectasia mutated
protein; CSB, Cockayne syndrome B protein; CYPs, cytochromes P450; Fe,
iron; G-6-P, glucose-6-phosphate; GSH, glutathione; GSSG, glutathione
disulfide; LPOs, lipoxygenases; NADP
þ
, nicotinamide adenine dinucleotide
phosphate; OGG1, oxoguanine glycosylase 1; PHSs, prostaglandin H synthases,
SOD, superoxide dismutase. Source: Modified from Wells et al. (2009b).
7.4.1.2 Signal Transduction ROS are widely implicated in highly
regulated cellular signal transduction pathways, which are selective to
different cell types and their subcellular organelles (Wells et al., 2009b)
(Figure 7.20). ROS signaling has been linked to numerous pathways
involved in cellular proliferation, differentiation, migration, and apo-
ptosis (Thannickal and Fanburg, 2000). ROS-mediated signal transduc-
tion has been attributed to hydrogen peroxide, which is less reactive and
