NIOSHTIC-2 Publications Search

Enhancement of chemical activation via radical-dependent mechanisms: an emerging concept in chemical-chemical interactions.

Authors
Trush MA; Thompson DC
Source
Oxygen radicals in biology and medicine. Simic MG, Taylor KA, Ward JF, Sonntag C eds. New York: Plenum Publishing Corporation, 1989 Jan; :739-744
NIOSHTIC No.
00190564
Abstract
Examples were given of chemical activation via radical dependent mechanisms and their pharmacologic and toxicologic implications were discussed. Studies were conducted using bleomycin-A2 (11116317) and butylated-hydroxytoluene (128370) (BHT). Bleomycin-A2, a glycopeptide antibiotic used in chemotherapy, is activated in the presence of iron and reactive oxygen species to an intermediate which can cleave DNA-deoxyribose, producing toxic base propenals. Enzymes associated with the endoplasmic reticulum or nuclear membrane catalyze this reaction. While the enhanced generation of activated bleomycin within tumor cells is beneficial, occurrence of this process in host cells is not. The administration of BHT results in pulmonary toxicity as reflected in damage to type-I alveolar cells. Microsomes from various animal tissues, including the lung, can enhance the activity of BHA. BHT is first converted to its radical intermediate and then to its electron reduced electrophilic species, BHT-quinone-methide. The subcutaneous administration of BHA resulted in an enhanced lung/body weight ratio indicating BHT induced lung damage.
Keywords
NIOSH-Grant; Cancer; Drug-interaction; Metabolic-study; Antineoplastic-agents; Laboratory-animals; Pulmonary-system-disorders
Contact
Environmental Health Sciences Johns Hopkins University 615 N Wolfe Street Baltimore, MD 21205
CAS No.
11116-31-7; 128-37-0
Publication Date
19890101
Document Type
Chapter
Editors
Simic MG; Taylor KA; Ward JF; Sonntag C
Funding Amount
36409
Funding Type
Grant
Fiscal Year
1989
Identifying No.
Grant-Number-R03-OH-01833
Priority Area
Asthma and Chronic Obstructive Pulmonary Disease; Disease and Injury; Pulmonary-system-disorders
Source Name
Oxygen radicals in biology and medicine
State
MD
Performing Organization
Johns Hopkins University, Baltimore, Maryland
Page last reviewed: October 8, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division