Genetic regulation of aryl hydrocarbon hydroxylase in primary cultures of fetal cells established from inbred strains of mice
Hitchins, V.M.; Laine, B.M.; Hutton, J.J.
Cancer Research 40(2): 424-431
1980
ISSN/ISBN: 0008-5472 PMID: 7356525 Document Number: 154470
Primary cultures of fetal cells were established from 6 inbred strains of mice to determine whether genes regulating induction of aryl hydrocarbon hydroxylase (AHH) in livers in vivo also function in fetal cells maintained in vitro. Fetal cells were cultured from 3 inbred mouse strains that are classified genetically as aromatic hydrocarbon responsive (A/J, C3H/HeJ and C57BL/6J), and 3 that are classified as aromatic hydrocarbon nonresponsive (AKR/J, DBA/2J and SWR/J). Responsive strains produce a high-affinity protein receptor for polycyclic hydrocarbons, whereas nonresponsive strains do not. The time course of the induction of AHH activity by 0.1 .mu.g 3-methylcholanthrene or 1.0 .mu.g benzanthracene/ml of media was followed from the time cells were plated until cells reached confluency. During exponential growth phase, AHH activity in basal and induced cells increased, reached a plateau and then gradually decreased as cells attained confluency and entered stationary growth phase. Fetal cells could be classified into 2 groups on the basis of whether they were from aromatic hydrocarbon-responsive or nonresponsive strains of mice. Ratios of induced AHH activity to basal AHH activity were determined during late exponential to early stationary growth phase. Values were near 1.0 for 3-methylcholanthrene-induced cells and 7-10 for benzanthracene-induced cells established from the 3 nonresponsive inbred strains of mice. Fetal cells cultured from the 3 responsive inbred strains of mice had ratios near 2.0 for 3-methylcholanthrene-induced cells and > 10 for benzanthracene-induced cells. AHH activities in basal and induced fetal cells were inhibited by 7,8-benzoflavone, indicating that the major type of AHH is predominantly of the nonhepatic type. The genes controlling aromatic hydrocarbon responsiveness in mouse livers in vivo apparently also function in nonhepatic fetal cells in vitro [AHH is suspected of being involved in tumor induction by activating hydrocarbon carcinogens.].