Exposure to cigarette tar inhibits ribonucleotide reductase and blocks lymphocyte proliferation.
Cigarette smoking causes profound suppression of pulmonary T cell responses, which has been associated with increased susceptibility to respiratory tract infections and decreased tumor surveillance. Exposure of human T cells to cigarette tar or its major phenolic components, hydroquinone and catechol, causes an immediate cessation of DNA synthesis without cytotoxicity. However, little is known of the mechanisms by which this phenomenon occurs. In this report we demonstrate that hydroquinone and catechol inhibit lymphocyte proliferation by quenching the essential tyrosyl radical in the M2 subunit of ribonucleotide reductase.
McCue
J M
JM
Department of Allergy and Clinical Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Link
K L
KL
Eaton
S S
SS
Freed
B M
BM
D002396:Catechols / Q000494:pharmacology; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D010947:Plants, Toxic; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D013638:Tars / Q000494:pharmacology*; D014026:Nicotiana; D014443:Tyrosine / Q000378:metabolism
D002396:Catechols; D004791:Enzyme Inhibitors; D005609:Free Radicals; D006873:Hydroquinones; D007166:Immunosuppressive Agents; D007502:Iron Chelating Agents; D013638:Tars; C024746:tobacco tar; D014443:Tyrosine; D004247:DNA; D012264:Ribonucleotide Reductases