Evidence of a direct relationship between the increase in the in vitro passage number of human non-small-cell-lung cancer primocultures and their chemosensitivity.

A pharmacologically relevant modelling was attempted for screening of new molecules potentially active against non-small-cell lung cancers (NSCLCs). It was in this way that we investigated the in vivo chemosensitivity firstly of three human NSCLCs grafted onto nude mice, secondly of their in vitro primocultures, and thirdly of the A427 and the A549 long-term cell lines obtained from the ATCC. Furthermore, the spontaneous development of the degree of chemosensitivity of the primocultures over their successive in vitro passages was compared with the development of the chromatin texture of the cancer cells. This chromatin texture was studied by means of the digital cell image analysis of Feulgen-stained nuclei. Our current experiments show that human non-small-cell lung cancers grafted onto nude mice possess a high level of chemoresistance. Such chemoresistance is conserved in vitro when these NSCLCs are adapted to grow as primocultures. Then, after only some in vitro passaging, the NSCLC chemoresistance quickly moved towards a high level of chemosensitivity, with a degree of sensitivity wholly similar to what was observed with respect to the long-term human lung cultures obtained from the ATCC. This reversion of chemoresistance in the NSCLC primocultures towards chemosensitivity occurred along with a specific transformation of their chromatin patterns, i.e. a marked increase in the frequency of the small dense chromatin clumps within the nucleus and a decrease of the larger ones.