Folate deficiency causes massive incorporation of uracil into human DNA (4 million per cell) and chromosome breaks. The likely mechanism is the deficient methylation of dUMP to dTMP and subsequent incorporation of uracil into DNA by DNA polymerase. During repair of uracil in DNA, transient nicks are formed; two opposing nicks could lead to chromosome breaks. Both high DNA uracil levels and elevated micronucleus frequency (a measure of chromosome breaks) are reversed by folate administration. A significant proportion of the U.S. population has low folate levels, in the range associated with elevated uracil misincorporation and chromosome breaks. Such breaks could contribute to the increased risk of cancer and cognitive defects associated with folate deficiency in humans.

https://www.pnas.org/content/pnas/94/7/3290.full.pdf

Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)61493-6.pdf

Post-splenectomy and hyposplenic states

Hematologic manifestations of celiac disease.

The Reticuloendothelial System

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jth.13813

Autoimmune heparin-induced thrombocytopenia.

We assessed splenic activity after splenectomy by interference phase microscopical examination of circulating red cells. Normal eusplenic children had a low number (less than 1 per cent) of red cells with surface indentations or "pits". About 20 per cent of red cells of children who had electively been subjected to splenectomy for hematologic indications were "pitted". Thriteen of 22 children who had had emergency splenectomy because of traumatic injury had a low percentage of "pitted" red cells, suggesting a return of splenic function. In five of these children a 99mTc sulfur colloid scan demonstrated multiple nodules of recurrent splenic tissue. In contrast to the prevailing opinion that splenosis is rare, we have found it to be a frequent occurrence. Return of splenic function may, in part, account for the low frequency with which overwhelming bacterial sepsis and meningitis have been documented after splenectomy for traumatic indications.

Karen Smith

Papers

The born-again spleen. Return of splenic function after splenectomy for trauma.

Methemoglobinemia as a complication of topical dapsone

Heparin-Induced Thrombocytopenia Presenting as Bilateral Adrenal Hemorrhages