Aryl hydrocarbon hydroxylase activity in mouse, rat, and human mammary tumors

Aryl hydrocarbon hydroxylase (AHH) activity was measured in microsomes from chemically induced and spontaneous mammary tumors of mice and rats and in 213 human breast tumors. Basal enzyme activities [pmol 3-hydroxybenzo(a)pyrene per mg protein per min] ranged from 0.05 to 0.5 for rat, 0.05 to 10 for mouse, and 0 to 40 for human tumors. For comparison, mean liver AHH activities were 13 in untreated rats and 100 in untreated mice. Thus, some human breast tumors had AHH activity exceeding that in rat liver. Injection of 80 mg beta-naphthoflavone per kg into tumor-bearing C3H/HeJ mice or Sprague-Dawley rats increased AHH activity to 10- to 70-fold over basal levels; there was no significant AHH induction in tumors from genetically "nonresponsive" DBA/2J or RF/J mice treated with beta-naphthoflavone, alpha-Naphthoflavone in the incubation flask inhibited AHH activity in some human breast tumors and stimulated activity in others, probably reflecting the presence of multiple forms of cytochrome(s) P-450 in the human tumor population. AHH activity in human tumors was not correlated with their estrogen receptor content. Since several drugs used in cancer treatment are substrates for polysubstrate monoxygenases, high levels of AHH activity in some human tumors may play a role in their response to chemotherapy.