Mercaptobenzothiazole allergenicity-role of the thiol group.
The rubber accelerator, 2-mercaptobenzothiazole (MBT), is known to cause allergic contact dermatitis (ACD), but the mechanism is unknown. The role of the thiol group in MBT's allergenicity was investigated in the present study. Guinea pigs were sensitized to MBT using a modified guinea pig maximization test (GPMT) and reactivity was assessed toward 2-mercaptobenzothiazole disulfide (MBTS), 2-hydroxybenzothiazole (HBT; thiol-substituted), 2-(methylthio)benzothiazole (MTBT; thiol-blocked), and benzothiazole (BT; thiol-lacking). MBT and MBTS, but not BT, HBT, or MTBT, elicited ACD in MBT-sensitized animals, demonstrating that the thiol group is critical to MBT's allergenicity. In addition, both MBT and MBTS were shown to inhibit both glutathione reductase and thioredoxin reductase, and thus contribute to the stability of MBT-protein mixed disulfides. It is concluded that the probable haptenation mechanism of MBT is through initial oxidation to MBTS with subsequent reduction to form mixed disulfides with proteins.
Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505-2888, USA.
Itai
I
Chipinda
Xing-Dong
XD
Zhang
Reuben H
RH
Simoyi
Paul D
PD
Siegel
D000704:Analysis of Variance; D000818:Animals; D052160:Benzothiazoles / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D003429:Cross Reactions; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000473:pathology; D004220:Disulfides / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006241:Haptens / Q000009:adverse effects* / Q000737:chemistry / Q000378:metabolism; D007114:Immunization / Q000379:methods; D010084:Oxidation-Reduction; D012408:Rubber / Q000009:adverse effects / Q000737:chemistry; D012867:Skin / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000009:adverse effects* / Q000032:analysis / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*
D052160:Benzothiazoles; D004220:Disulfides; D006241:Haptens; D013438:Sulfhydryl Compounds; C005563:captax; C028000:dibenzothiazyl disulfide; D012408:Rubber; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase