AN EXPERIMENTAL-MODEL OF MULTISTEP LARYNGEAL CARCINOGENESIS - COMBINED EFFECT OF HUMAN PAPILLOMAVIRUS TYPE-16 GENOME AND N-METHYL-N'-NITRO-N-NITROSOGUANIDINE
K. Tsutsumi et al., AN EXPERIMENTAL-MODEL OF MULTISTEP LARYNGEAL CARCINOGENESIS - COMBINED EFFECT OF HUMAN PAPILLOMAVIRUS TYPE-16 GENOME AND N-METHYL-N'-NITRO-N-NITROSOGUANIDINE, Acta oto-laryngologica, 1996, pp. 89-93
This report describes the two-step in vitro transformation of human la
ryngeal epithelial cells (HLEC cells). Primary cultured HLEC cells wer
e first transfected with cloned full-length human papillomavirus type
16 DNA, and two immortalized cell lines (HLEC-16 cell lines) were sele
cted by subculturing transfected cells that continued to proliferate.
The HLEC-16 cell lines were not tumorigenic in nude mice, and did not
proliferate well in a culture medium containing a physiological level
of calcium (Dullbecco's minimum essential medium supplemented with 10%
fetal bovine serum = DMEM + 10%FBS). The HLEC-16 cell lines were seco
ndarily exposed to N-methyl-N'-nitro-N-nitrosoguanidine, and several p
roliferating colonies were isolated in DMEM + 10%FBS. Among these calc
ium/serum-resistant cell colonies, one colony exhibited enhanced proli
feration capacity in nude mice. These results support the hypothesis t
hat human laryngeal epithelial cells may be the target for neoplastic
transformation by a combined effect of human papillomaviruses and chem
ical carcinogens.