Alteration of radiation-sensitive processes associated with cancer and longevity by dietary 2-mercaptoethanol

Abstract

Background: Previous results demonstrated dietary 2-mercaptoethanol (2-ME) delayed appearance of cancer in certain murine strains. In addition, it had a benefit not found with other organosulfurs, in that it completely prevented spontaneous development of cancer in BXSB-Yaa + over an entire lifespan.

Aims: These benefits raise the question: What, if any, alteration of radiation-induced tumorigenesis would 2-ME impart that may differ from that of other sulfur antioxidants? This is relevant based on the extensive use of radiation in diagnoses and therapy and 2-ME's superior in vitro and in situ immune enhancement properties.

Materials and methods: This was addressed by exposing long-lived, B10.A (4R) mice to sublethal, 5.5 Gy ionizing gamma-rays and then tumor development monitored over a lifetime.

Statistical analysis: Two-tailed P-values were determined using the Fischer's Exact Test.

Results: The only tumors detected were mammary and only in animals that were both exposed to radiation and not treated with 2-ME. The 43% incidence differed significantly from the absence of tumors in non-irradiated mice that were or were not exposed to 2-ME and in those irradiated and treated daily with 2-ME, irrespective of whether treatment was started prior to or post irradiation. However, quite unexpectedly, radiation shortened longevity 29% from undefined causes, including cancer, in animals pretreated with 2-ME; longevity was not altered in those not pretreated or if treatment was started post-irradiation.

Conclusions: The findings have relevance for cancer prevention and the controversy relative to ''long term survival/safety'' of currently used antioxidants as free radical scavengers in humans undergoing radiotherapy.

Figure 1. Survival of control and gamma-radiated B10.A(4R) mice on and off dietary supplemented 2-Me compared to those that had their 2-Me treatment reversed at 288 days

Panel A. Mice in this panel were never exposed to 2-Me at any time of their life. At 287 days of age, one group was irradiated (○----○); the other group was not (○ - ○). (+) designates animals with mammary tumor. Panel B. Mice in this panel were on water devoid of 2-Me for 288 days, at which time they were all switched to 2-Me; one group was also irradiated at 287 days of age (○----○). Panel C. Mice in this panel were started on 2-Me at 90 days of age, and then continued for the remained of their lives. At 287 days of age, one group was irradiated (○----○); the other group was not (○ - ○). Panel D. Mice in this panel were on 2-Me for 288 days, at which time they were all switched to water devoid of 2-Me; one group was irradiated at 287 days of age. (○----○); the other was not (○ - ○)