AROMATIC HYDROCARBON RECEPTOR IN CULTURED FETAL CELLS FROM C57BL 6J AND DBA/2J MICE - SIMILARITY IN MOLECULAR-MASS TO RECEPTORS IN ADULT LIVERS/

In liver of adult responsive C57BL/6J (B6) mice the aromatic hydrocarb on receptor (AHR) has high affinity for specific halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as w ell as nonhalogenated aromatic hydrocarbons (PAHs), such as benz[a]ant hracene (BA) or 3-methylcholanthrene (MC). In livers of adult nonrespo nsive DBA/2J (D2) mice TCDD binds to a low-affinity variant form of AH R. Both TCDD and MC induce aryl hydrocarbon hydroxylase (AHH) in adult B6 mice, whereas adult D2 mouse liver is nonresponsive to MC. In feta l cell cultures derived from D2 mice AHH is induced by PAHs such as MC or BA, and these PAHs bind to cytosolic AHR (P.A. Harper, C.L. Colas, and A.B. Okey. Mel. Pharmacol. 40: 818-826, 1991). We compared AHR fr om fetal cell cultures with AHR from adult livers to determine whether there was some structural difference in receptors expressed in fetal cell culture that might permit cells from ''nonresponsive'' mice to re spond to PAHs. The apparent molecular mass of AHR from cells cultured from 18-day fetuses is identical with that from adult liver within eac h strain of inbred mice tested (M(r) similar to 95 kDa in B6 and simil ar to 105 kDa in D2 mice). The AHR in D2 fetal cells was able to activ ate a transfected chloramphenicol acetyltransferase linked to a dioxin -responsive element nucleotide sequence (DRE-CAT) when the cells were treated with TCDD or MC. The potency of CAT expression in D2 fetal cel ls was similar to that in B6 fetal cells. Our data suggest that the re sponsiveness of fetal cells from ''nonresponsive'' mice is likely medi ated by AHR in these cells but is not due to expression of a different allelic form of AHR ligand-binding subunit in fetal cells versus adul t liver.