# CARCINOGEN INDUCTION OF INFINITE LEFESPAN IN HUMAN CELLS

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 1992 · $218,459

## Abstract

Since cancer is fundamentally a human problem, it is critical to
understand the process as related to the human species.  Studies
on the mechanisms of rodent cell malignant transformation in
vitro have been elegantly carried out and allow detailed analysis
of the process of carcinogenesis in these species.  Unfortunately,
the malignant transformation of human cells in culture does not
occur spontaneously or as a result of carcinogen treatment,
despite intensive work by many investigators, including our group.
The few reports of the malignant transformation of human cells in
vitro that have been published seem to involve a large element of
chance.  However, it is now possible to induce human fibroblasts
to express all but one of the common phenotypic changes
characteristic of the transformed rodent fibroblasts.  The
property of unlimited lifespan (UL) often referred to as
"immortality" is never seen.  This may be because rodent
fibroblasts and human fibroblasts are fundamentally different,
perhaps reflecting the great difference in lifespan of these
species.  As discussed in the proposal, there are reasons to believe
that this is not true.  It seems much more likely that the failure
to obtain a UL human fibroblast is an artifact of cell culture.
Therefore, this proposal is an all out effort to develop methods to
reproducibly induce UL human fibroblasts.  At the same time,
three diploid UL human fibroblast cell lines, the only ones know to
us, will be used to determine the role of various other changes in
the multistepped process of malignant transformation.

Using fibroblast cell lines derived from normal persons and from
patients with Bloom's syndrome and Fanconi's anemia, we will try
to induce cells with unlimited lifespans.  To do so, we will grow
the cells under conditions of increased oxygen tension to induce
clastogenic effects.  We will also expose normal fibroblasts
repeatedly to the anti 7,8-diol-9,10-epoxide of benzo(a)pyrene
because exposure of Syrian hamster fibroblasts to this carcinogen
led to UL.  We will select these series of treated populations for
nonsenescing cells, using conditions that avoid metabolic
cooperation between senescing and nonsenescing cells.

While the above experiments are in progress we will expose three
fibroblast cell lines that have already acquired unlimited lifespan
(HUT 11, HUT, 12 and LGIvmyc1) to carcinogens in order to
induce them to acquire the rest of the series of
tumorcellrelated characteristics in a stepwise fashion and
determine which combination of traits confers on them the ability
to form tumors.  We will also determine how fibroblasts derived
from human fibromas and low grade maligancies differ from
normal cells and from fibrosarcomaderived cells since they may
represent intermediates on the path to malignancy.

## Key facts

- **NIH application ID:** 3123009
- **Project number:** 9R01AG011026-14
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **SAM.gov UEI:** R28EKN92ZTZ9
- **Principal Investigator:** J JUSTIN MCCORMICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $218,459
- **Award type:** 9
- **Project period:** 1992-04-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123009

## Citation

> US National Institutes of Health, RePORTER application 3123009, CARCINOGEN INDUCTION OF INFINITE LEFESPAN IN HUMAN CELLS (9R01AG011026-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123009. Licensed CC0.

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