CYP1A Induction and Human Risk Assessment: An Evolving Tale of In Vitro and In Vivo Studies

Details

• Personal Author:
  Lu AYH ; Ma Q
• Description:
  CYP1A1 and 1A2 play critical roles in the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines/amides (HAAs), respectively, to electrophilic reactive intermediates, leading to toxicity and cancer. CYP1As are highly inducible by PAHs and halogenated aromatic hydrocarbons via aryl hydrocarbon receptor-mediated gene transcription. The impact of CYP1A induction on the carcinogenic and toxic potentials of environmental, occupational, dietary, and therapeutic chemicals has been a central focus of human risk evaluation and has broadly influenced the fields of cancer research, toxicology, pharmacology, and risk assessment over the past half-century. From the early discovery of CYP1A induction and its role in protection against chemical carcinogenesis in intact animals, to the establishment of CYP1A enzymes as the principal cytochromes P450 for bioactivation of PAHs and HAAs in in vitro assays, to the recent realization of an essential protective role of CYP1A in benzo[a]pyrene-induced lethality and carcinogenesis with CYP1A knockout mice, the understanding of the interrelation between CYP1A induction and chemical safety has followed a full circle. This unique path of CYP1A research underscores the importance of whole animal and human studies in chemical safety evaluation. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Hazardous Substances Health Care Facilities Workforce And Services Neoplasms Occupational Health Risk Assessment Risk Factors Safety Safety Management Toxicology

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• Keywords:
  Analytical-processes Animal-studies Bioactivation Cancer-rates Chemical-analysis Chemical-composition Chemical-indicators Chemical-properties Chemical-synthesis Hazardous-materials Health-hazards Health-protection Health-services Humans Pharmacology Risk-analysis Risk-factors Safety-education Safety-measures Safety-monitoring Safety-practices Safety-research Toxic-effects Toxic-gases Toxic-vapors Toxicopathology

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• ISSN:
  0090-9556
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  New Jersey ; OSHA Region 2 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  35
• Issue:
  7
• NIOSHTIC Number:
  nn:20032330
• Citation:
  Drug Metab Dispos 2007 Jul; 35(7):1009-1016
• Contact Point Address:
  Qiang Ma, Receptor Biology Laboratory, TMBB/HELD/NIOSH/CDC, Mailstop 3014, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  qam1@cdc.gov
• Federal Fiscal Year:
  2007
• Peer Reviewed:
  True
• Source Full Name:
  Drug Metabolism and Disposition
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:08533534d7a5d3499a965bc7d16a6c46cb40bba4f933721ef7583d25f6bd367c7e99115f5c484d3c36a4030f1758ae30716b523f6b60205cfe1790de0fe6bf95
• Download URL:
  https://stacks.cdc.gov/view/cdc/186350/cdc_186350_DS1.pdf
• File Type:
  [PDF - 129.01 KB ]