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

Details

• Personal Author:
  Thompson DC ; Trush MA
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Antineoplastic Agents Energy Metabolism Laboratories Neoplasms Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  NIOSH-Grant; Cancer; Drug-interaction; Metabolic-study; Antineoplastic-agents; Laboratory-animals; Pulmonary-system-disorders
• ISBN:
  9781468455700
• Publisher:
  Plenum Publishing Corporation
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Book
• Place as Subject:
  Maryland ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• NIOSHTIC Number:
  nn:00190564
• Citation:
  Oxygen radicals in biology and medicine. Simic MG, Taylor KA, Ward JF, Sonntag C eds. New York: Plenum Publishing Corporation, 1988 Jan; :739-744
• Contact Point Address:
  Environmental Health Sciences Johns Hopkins University 615 N Wolfe Street Baltimore, MD 21205
• CAS Registry Number:
  2,6-Di-tert-butyl-4-methylphenol (CAS RN 128-37-0) ; Bleomycin A2 (CAS RN 11116-31-7)
• Editor(s):
  Simic MG; Taylor KA; Ward JF; Sonntag C
• Federal Fiscal Year:
  1988
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  Johns Hopkins University, Baltimore, Maryland
• Peer Reviewed:
  False
• Start Date:
  19830701
• Source Full Name:
  Oxygen radicals in biology and medicine
• End Date:
  19850630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/247711/cdc_247711_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]