Endotoxin causes Genotoxic DNA Strand Breaks

Cancer caused by a sugar in Endotoxin is understood at molecular level.

I have written about Endotoxin causing Turbo Cancer via its impact on p53¹ Tumor-associated macrophages² and the Warburg effect.³

Now let us look at Endotoxin causing Cancer via direct hit on your DNA.

The Inner Core of Endotoxin has been studied in great detail and provides another toxin, namely the sugar β-ADP-heptose (Adenosine 5'-diphosphate-L-glycero-D-mannoheptose), that creates DNA strand breaks.

Here is a nice figure illustrating the biosynthesis of Endotoxin showing the Heptose sugars from a recent review that lists 92 references.⁴

The caption reads:

Figure 1. Biosynthesis of lipopolysaccharide (LPS, Endotoxin).

(a) Structure of LPS.

(b) Schematic illustration of the ADP-heptose synthesis pathway: GmhA (sedoheptulose 7-phosphate isomerase); bifunctional HldE (D-β-D-heptose 7-phosphate kinase and D-β-D-heptose 1-phosphate adenylyltransferase); GmhB (D-glycero-α,β-D-manno-heptose 1,7-bisphosphate 7-phosphatase); HldD (ADP-D-β-D-heptose epimerase); and the enzymes present in the Neisseria species. In green: HldA (β-D-heptose-7-phosphate kinase) and HldC (β-D-heptose-1-phosphate adenosyltransferase). The nomenclature for genes coding enzymes present in H. pylori is shown in red, and the equivalent names for enzymes are shown on the far right of the pathway.

Readers will recall the supertoxic component Lipid A.

I will add to this article and encourage readers to tell me if other Substackers have covered this topic in depth.