Enzymatic Analysis of cDNA-Expressed Human CYPIAI, CYPlA2, and CYPIBI with 7-Ethoxyresorufin as Substrate
Bibliographic record
Abstract
The human CYP1 family consists of at least three proteins, CYP1A1, CYP1A2, and CYP1B1 ( 1 ), CYP1A1 is absent or present at very low levels in human liver ( 2 , 3 ), but its expression is readily detectable in lung ( 4 , 5 ). By contrast, CYP1A2 is constitutively expressed in human liver ( 2 , 3 ) and is absent in lung ( 4 , 5 ). CYP1B1 is primarily an extrahepatic P450, as suggested by the findmg that CYP1B1 mRNA is present in much greater abundance in tissues such as kidney, prostate, and breast than in liver ( 6 ). Exposure to polycyclic aromatic hydrocarbons such as those found in cigarette smoke induces the expression of both CYP1A1 and CYP1A2 ( 3 , 7 ). CYP1B1 is also inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as demonstrated by cell-culture experiments ( 8 , 9 ). The chemical inhibitor a-naphthoflavone, which is a potent inhibitor of CYP1A1 and CYP1A2 ( 10 ), also inhibits CYP1B1 and with semilar efficacy and potency ( 11 ). cDNA-expressed CYP1A1, CYP1A2 and CYP1B1 are each active in the oxidation of theophylline ( 11 ), caffeine ( 11 , 12 ), estradiol ( 13 , 14 ), benzo[a]pyrene ( 11 ) and 7-ethoxyresorufin ( 11 ). With 7-ethoxyresorufin as substrate, the rank order of specific activity (pmol/min/nmol P450) is CYP1A1 > CYP1B1 > CYP1A2 ( 11 ). 7-Ethoxyresorufin O -deethylation activity can be a useful and convenient catalytic monitor when conducting a comparative study using a panel of these three recombinant CYP1 enzymes ( see Note 1 ). Immunoinhibition experiments with inhibitory CYP1A-selective antibodies have suggested that CYP1A2 is a major contributor to 7-ethoxyresorufin O -deethylase activity in human liver microsomes ( 15 , 16 ). These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".