Hexose uptake in 7,12-dimethylbenz(a)anthracene-preexposed rat tracheal epithelial cells during the progression of neoplasia.
Hexose uptake during the progression of neoplasia in rat tracheal epithelial cells was studied by measuring the uptake of 2-deoxy[3H]glucose (2-dGlc) in nontumorigenic (C-18) and tumorigenic (T-8, 1000-WT) rat tracheal epithelial cell lines with varying degrees of cell association as well as in: normal primary cell cultures (NPC) derived from explants of nonexposed tracheas; selected primary cell cultures (SPC) generated from explants of 7,12-dimethylbenz(a)anthracene-treated tracheal implants; and primary tumor cell cultures (TPC) derived from explants of 7,12-dimethylbenz(a)anthracene-induced tracheal carcinomas. The latter two groups represented cells from earlier and late stages in the progression of neoplasia, respectively, and each displayed an in vitro growth advantage that allowed for their survival and growth in medium devoid of supplements of pyruvate and insulin. This property was used in this study to select the carcinogen-altered cells from neighboring normal cells. Uptake of 2-dGlc per microgram of DNA was similar in subconfluent cultures of all cell lines. At confluency, uptake per microgram of DNA was reduced markedly (greater than 3-fold) in C-18 cells but it was reduced only 1.3-fold in T-8 cells and 1.6-fold in 1000-WT cells. Hexose uptake was further reduced in T-8 and 1000-WT cell cultures generated as outgrowths from explants of denuded tracheas bearing a reestablished epithelium from each cell line. Under these conditions, T-8 cells retained higher 2-dGlc uptake than did C-18, but uptake by 1000-WT was lower, indicating that tissue-like cell associations have a profound effect on hexose uptake in these epithelial cells. Results were generally similar when uptake was expressed per mg of protein although, in several instances, the interpretation of uptake data was affected by differences in the protein content between cultures (assessed by comparing protein:DNA ratios). Compared to NPC, hexose uptake was lower in SPC and one group of TPC. A second group of TPC, characterized by loose cell associations and much cell overlapping, had distinctly higher 2-dGlc uptake than did controls. Comparable results in these primary cultures were also observed when the number of cells per culture was used as a reference for 2-dGlc uptake. Under conditions of glucose deprivation, hexose uptake was increased in NPC and SPC. The production of lactic acid in each type of culture was dependent on the level of glucose in the medium, and this was nearly 2-fold greater in NPC than in SPC.(ABSTRACT TRUNCATED AT 400 WORDS)
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009924:Organ Culture Techniques; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014134:Tracheal Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D001551:Benz(a)Anthracenes; D003837:Deoxy Sugars; D015127:9,10-Dimethyl-1,2-benzanthracene; D003847:Deoxyglucose