Induction of immortality is an early event in malignant transformation of mammalian cells by carcinogens

Abstract

Limited lifespan in normal diploid mammalian cells in culture is well documented^1–3 and there is evidence that it is also a property of normal tissues serially transplanted in vivo^4,5. In contrast, in favourable growth conditions, cells derived from tumours or premalignant tissue often exhibit unlimited proliferative potential (immortality) both in vitro and in vivo^2,4,6–10. Malignant transformation of diploid cells in culture by carcinogens has been clearly demonstrated in several laboratories^2,11–13. However, although it has been frequently reported that establishment in culture is one of many alterations in cell behaviour associated with transformation, the induction of immortality and its role in malignancy have not previously been subjected to serious scientific examination. Here, we show that treatment of Syrian hamster cell cultures with carcinogenic chemicals can induce rare immortal variants, the progeny of which then frequently progress to anchorage independence and malignancy after a further period of growth. In addition, by studying the properties of cell lines that are either immortal or anchorage-independent but not both, we have obtained evidence that immortality, although insufficient by itself, may be a prerequisite for malignant transformation.