NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes
IR@IICB: CSIR-Indian Institute of Chemical Biology, KolkataView Archive Info
NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint
with Marginal Vitamin C Deficiency Causes Cigarette
Smoke Induced Myelodysplastic Syndromes
Chatterjee, Indu B
Infectious Diseases and Immunology
Background: The etiology of myelodysplastic syndromes (MDS) is largely unknown. Exposure to cigarette smoke (CS) is
reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(P)H-quinone: oxidoreductase
1 (NQO1) increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient
guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin
C deficiency might produce MDS in CS-exposed guinea pigs.
Methodology and Principal Findings: Here we show that CS exposure for 21 days produces MDS in guinea pigs having
deficiency of NQO1 (fed 3 mg dicoumarol/day) conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day). As
evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory
cytopenia with unilineage dysplasia (RCUD): refractory anemia; refractory thrombocytopenia that is associated with ring
sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+) cells
and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS
but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all
the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS
vitamin C becomes ineffective.
Conclusions and Significance: CS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal
vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our
results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be
at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS.
Das, Archita and Dey, Neekkan and Ghosh, Arunava and Das, Tanusree and Chatterjee, Indu B (2011) NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes. PLoS One, 6 (5). 01-12.