PMID- 7248171 OWN - NLM STAT- MEDLINE DCOM- 19810922 LR - 20181113 IS - 0007-1021 (Print) IS - 0007-1021 (Linking) VI - 62 IP - 3 DP - 1981 Jun TI - Tritiated-thymidine-induced increased DNA content and irreversible differentiation in a human melanoma cell line. PG - 289-96 AB - When cultured in the presence of 2.0 microCi/ml (methyl-3H)thymidine (3H-TdR) the growth rate of 6 human melanoma lines and 1 subline progressively slowed then stopped, a change that was accompanied by loss of reproductive viability as assessed by colony formation in agar, but unaccompanied by a comparable inhibition of thymidine incorporation. In all cases increases in cell size, nuclear size and DNA content were observed. In 1 cell line only, MM96, these changes were accompanied by a profound increase in morphological differentiation. Despite this MM96 did not show increased differentiation in response to 2 x 10(-7) M alpha melanocyte stimulating-hormone (alpha MSH), which in fact stimulated growth, or in response to 10(-3) M N6,O2'-dibutyryl adenosine 3':5'-monophosphate (db-cAMP), 10(-3) M theophylline or 5 x 10(-4)M guanosine-5'-triphosphate (GTP), all of which retarded growth. With none of the cell lines was differentiation increased in response to 10(-3)M db-cAMP although in each case growth was retarded. These results reinforce the importance of colony assays vs DNA synthesis studies in assessing reproductive viability and show that supra-reproductively lethal levels of 3H-TdR can by-pass defects in the differentiation pathway of at least one, but not all, human melanoma cell lines. FAU - Sheridan, J W AU - Sheridan JW FAU - Simmons, R J AU - Simmons RJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Exp Pathol JT - British journal of experimental pathology JID - 0372543 RN - 0 (DNA, Neoplasm) RN - 958-74-7 (methylthymidine) RN - VC2W18DGKR (Thymidine) SB - IM MH - Cell Count MH - Cell Differentiation MH - Cell Line MH - DNA, Neoplasm/*biosynthesis MH - Humans MH - Melanoma/*metabolism/pathology MH - Mitotic Index MH - Thymidine/analogs & derivatives/metabolism MH - Time Factors PMC - PMC2041686 EDAT- 1981/06/01 00:00 MHDA- 1981/06/01 00:01 PMCR- 1981/06/01 CRDT- 1981/06/01 00:00 PHST- 1981/06/01 00:00 [pubmed] PHST- 1981/06/01 00:01 [medline] PHST- 1981/06/01 00:00 [entrez] PHST- 1981/06/01 00:00 [pmc-release] PST - ppublish SO - Br J Exp Pathol. 1981 Jun;62(3):289-96.