TABLE 1

P values comparing Tac or MDZ metabolic activity between cell lines

P values were calculated based on the paired two-sample t test comparing between each cell line. Substrates and products were quantified by liquid chromatography-mass spectrometry of the media from the cell cultures.

Cell Lines ComparedP Values
SubstratesProducts
TacMDZ1-OH MDZ4-OH MDZ
HuH-7 a *3/*3 vs. CYP3A5 *1/*3 sdb 5.4 × 10−32.4 × 10−52.3 × 10−67.3 × 10−4
HuH-7 *3/*3 vs. CYP3A5 *1/*1 ddc2.7 × 10−35.3 × 10−48.6 × 10−52.7 × 10−4
HuH-7 *3/*3 vs. CYP3A5 *1/*3 pmd2.7 × 10−25.0 × 10−73.8 × 10−81.3 × 10−3
CYP3A5 *1/*3 sd vs. CYP3A5 *1/*1 dd1.0 × 10−23.6 × 10−13.5 × 10−21.6 × 10−2
CYP3A5 *1/*3 sd vs. CYP3A5 *1/*3 pm5.3 × 10−25.3 × 10−11.8 × 10−39.4 × 10−1
CYP3A5 *1/*1 dd vs. CYP3A5 *1/*3 pm3.1 × 10−24.1 × 10−12.0 × 10−32.4 × 10−2
  • a HuH-7 was the parental cell line with CYP3A5 *3/*3 alleles.

  • b CYP3A5 *1/*3 sd was a bioengineered cell line with the CYP3A5 *1 allele made by deletion of a splice acceptor on one of the alleles.

  • c CYP3A5 *1/*1 dd was a bioengineered cell line with both CYP3A5 *1 alleles made by deletion of a splice acceptor on two of the alleles.

  • d CYP3A5 *1/*3 pm was a bioengineered cell line with the CYP3A5 *1 allele made by a point mutation of a splice acceptor on one of the alleles.