VOL. 7, No. 1/2, December 2011

T. Abo, et al. [2011] Med. Hypotheses Res. 7: 53−56.

Metabolic Conditions, Hypothermia, and Hypoxia
Induced by Continuous Stress Are More Often
Associated with Carcinogenesis than Known Carcinogens

Toru Abo*, Mayumi Watanabe, Hiroaki Matsumoto,
Chikako Tomiyama and Tomoyo Taniguchi

Department of Immunology, Niigata University School of Medicine, Niigata 951-8510, Japan
(T.A., M.W., H.M., T.T.), and School of Health Sciences, Faculty of Medicine, Niigata
University, Niigata 951-8518, Japan (C.T.)

Abstract. Many investigators believe that carcinogenesis occurs in cells as genetic
mutational events induced by carcinogens such as ultraviolet rays, food additives, nuclear
radiation, and air pollution. However, in cancer clinics it is typically difficulty to determine
whether such carcinogens actually cause cancer in patients. On the other hand, cumulative
evidence has revealed that cancer cells produce energy mainly through glycolysis, and such
cells contain few mitochondria. There is a question as to how genetic mutations, carcinogens,
and glycolysis in cancer cells are associated with each other. To address this question, we
propose a new concept on carcinogenesis, namely, the concept of “adaptive response of
glycolysis to adverse internal conditions induced by stress”. When humans and animals are
exposed to severe stress, they can undergo hypothermia, hypoxia, and hyperglycemia.
Related factors in these processes include catecholamines induced by sympathetic activation,
and glucocorticoids secreted by adrenal glands. This internal environment is beneficial for the
anaerobic glycolysis pathway. However, if stress continues unabated, this environment
suppresses oxidative phosphorylation in mitochondria. Among normally dividing cells with
fewer mitochondria, adaptive responses occur gradually. After multi-step genetic mutations,
some cells are able to change their genetic properties to overcome hypothermia and hypoxia.
These are typically cancer cells. The concept proposed here may provide some explanation as
to how external environmental factors interplay with endogenous cellular metabolism to
promote carcinogenesis.

* Correspondence: Dr. Toru Abo, Department of Immunology, Niigata University School of
Medicine, Niigata 951-8510, Japan. FAX: +81 25 227 0766. E-MAIL: