Biochemical Genetics

, Volume 15, Issue 7–8, pp 723–740 | Cite as

Genetics of aryl hydrocarbon hydroxylase induction in mice: Response of the lung to cigarette smoke and 3-methylcholanthrene

  • R. K. Abramson
  • B. A. Taylor
  • D. Tomlin
  • J. J. Hutton


When mice from different inbred strains are injected intraperitoneally with 3-methylcholanthrene (MC), the activity of aryl hydrocarbon hydroxylase (AHH) rapidly increases in livers of some strains but not others. AHH plays a role in the metabolism of polycyclic hydrocarbons. Alleles at a small number of loci account for most of the variation in inducibility of hepatic AHH among mice, when MC is used as the inducing agent. Cigarette smoke is a common source of carcinogenic polycyclic hydrocarbons in the environment. Since some of the hydrocarbons in cigarette smoke are metabolized by AHH, the activity of AHH in tissues may affect the carcinogenicity of smoke in those tissues. The purpose of these experiments was to see whether induction of AHH in lung in response to cigarette smoke is regulated by the same genes that regulate induction of AHH in liver in response to MC. Mouse strains AKR/J and C57L/J and six recombinant inbred (RI) lines derived from them were tested for the response of AHH in lung and liver to parenteral MC or inhalation of cigarette smoke. Inducibility (the ratio of MC-induced AHH activities to basal AHH activities) in liver from MC-treated RI lines is bimodal and compatible with Mendelian segregation of genes at a small number of loci. Increased activities of AHH in MC-treated liver are associated with increased ability to metabolize BP and whole smoke condensates to mutagens detected by Salmonella typhimurium TA1538. Inducibility of AHH in lung in response to MC is not bimodal, and no definite conclusion about the number of loci can be made. When actual levels of AHH activity are considered, following the administration of MC as inducing agent, there is a correlation (r=0.89, p<0.01) between AHH levels in liver and lung, suggesting that some genes affecting liver also affect lung. Basal and MC-induced AHH levels in lung are also correlated (r=0.86, p<0.01). Mice with high basal activities have two to threefold higher levels of AHH after MC treatment than do mice with low basal activities. Induction of AHH in pulmonary tissues occurs in all mice after either parenteral MC or smoke inhalation. In contrast to MC treatment, AHH activities in lungs following smoke inhalation are not correlated with AHH levels in liver after MC (r=0.49) and are only weakly correlated with basal (r=0.66, 0.05<p<0.10) pulmonary levels. The correlation between MC-induced and smoke-induced AHH activities in lung is weak (r=0.63, 0.05<p<0.10). We conclude that the genetic regulation of AHH activity in lung is not as simple as the genetic regulation of AHH activity in liver, especially when complex inducing agents such as cigarette smoke are used.

Key words

aryl hydrocarbon hydroxylase, gene loci controlling cigarette smoke mice lung liver 3-methylcholanthrene 


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Copyright information

© Plenum Publishing Corp 1977

Authors and Affiliations

  • R. K. Abramson
    • 1
  • B. A. Taylor
    • 2
  • D. Tomlin
    • 1
  • J. J. Hutton
    • 1
  1. 1.Medical Service, VA Hospital, and Department of MedicineUniversity of KentuckyLexington
  2. 2.The Jackson LaboratoryBar Harbor

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