Cell size, body size and Peto’s paradox

Abstract

Carcinogenesis is one of the leading health concerns afflicting presumably every single animal species, including humans. Currently, cancer research expands considerably beyond medicine, becoming a focus in other branches of natural science. Accumulating evidence suggests that a proportional scale of tumor deaths involves domestic and wild animals and poses economical or conservation threats to many species. Therefore, understanding the genetic and physiological mechanisms of cancer initiation and its progression is essential for our future action and contingent prevention. From this perspective, I used an evolutionary-based approach to re-evaluate the baseline for debate around Peto’s paradox. First, I review the background of information on which current understanding of Peto’s paradox and evolutionary concept of carcinogenesis have been founded. The weak points and limitations of theoretical modeling or indirect reasoning in studies based on intraspecific, comparative studies of carcinogenesis are highlighted. This is then followed by detail discussion of an effect of the body mass in cancer research and the importance of cell size in consideration of body architecture; also, I note to the ambiguity around cell size invariance hypothesis and hard data for variability of cell size across species are provided. Finally, I point to the new research area that is driving concepts to identify exact molecular mechanisms promoting the process of tumorigenesis, which in turn may provide a proximate explanation of Peto’s paradox. The novelty of the approach proposed therein lies in intraspecies testing of the effect of differentiation of cell size/number on the probability of carcinogenesis while controlling for the confounding effect of body mass/size.

Revealing endogenous conditions for Peto’s paradox via an ordinary differential equation model

“…Lastly, it is not our intention to solely attribute cancer development to intrinsic factors while disregarding other potential contributing factors. We are also aware of arguments suggesting the involvement of cell size (Maciak 2022 ; Maciak & Michalak 2015 ; Savage et al 2007 ), and the need for additional considerations when establishing a linear relationship between cell number and animal size. Overall, we recognize that Peto’s paradox is a complex phenomenon, and a combination of undiscovered factors may have contributed to this intriguing phenomenon.…”

Kimura’s Theory of Non-Adaptive Radiation and Peto’s Paradox: A Missing Link?

“…One resolution of the paradox—among many other hypotheses—has proposed that species with larger body sizes produce less reactive oxygen species (ROS), which damage DNA, proteins, and lipids. Genome size, however, might also play a role across broad taxonomic groups that range from short lived invertebrates, which have among the smallest animal genomes, to long-lived vertebrates, which have, comparatively speaking, substantially larger genomes [ 22 ]. Larger genomes result in larger cells that are consequently expected to have lower metabolic rates.…”

Парадокс Пето: Обзор Исследований

“…Согласно одной их гипотез Пето количество клеток в организме прямо пропорционально его размеру. Но исследования показывают, что с увеличением размеров организма увеличивается и размер клеток [21].…”

“…В статье 2022 года [21] сравнивались характеристики крыс из искусственно отобранных линий с высоким и низким BMR -базовым уровнем метаболизма. Крысы с высоким BMR показали ослабление иммунного ответа [27], усиление окислительного повреждения [28], усиление накопления тяжёлых металлов [29], увеличение заболеваемости колоректальным раком.…”