Microsoft Word c in Memoriam Dr ito doc

---

 

1

In Memoriam: Honorary Member Nobuyuki Ito, MD, PhD, 1928-2010 

 

Recently the scientific world, particularly 

toxicologic pathology, lost one of its great leaders, 

Nobuyuki Ito, MD, PhD, who passed away on October 

6, 2010 in Nagoya, after nearly 5 years battling illness. 

He was 81. 

 

In his academic life, Dr. Ito left behind a 

legacy of leadership and advancement of toxicologic 

pathology, toxicology, and research on chemical 

carcinogenesis. He received the 2005 Education Award 

from the Society of Toxicology celebrating recognition 

of his lifelong contributions to scientific and 

professional education. Dr. Ito began his pioneering 

efforts in toxicology education 35 years ago when he 

established an extensive teaching and training program 

for toxicologists at the Department of Pathology, 

Nagoya City University Medical School. He trained 

two generations of toxicologists and toxicologic 

pathologists in Japan and several from other countries, 

first as Chairman of the Department, then as Dean of 

the Medical School and lastly as President of the 

University. Dr. Ito and his students and senior 

scientists have made significant contributions to risk 

assessment and regulation of chemicals and food 

additives in Japan and internationally. His works in the 

field of histogenesis and modulation of the neoplastic 

process and on antioxidants in anti-carcinogenesis 

have been acknowledged by many societies, including 

the Princess Takamatsu Cancer Research Fund, the 

Japanese Cancer Association, and the International 

Federation of Societies of Toxicologic Pathology. 

During his distinguished career at Nagoya City 

University Medical School. Dr. Ito authored and 

co-authored with his numerous students and associates 

more than 600 peer-reviewed scientific publications. 

His former students, numbering more than 100, are in 

prestigious and important positions around the world, 

continuing his task of educating toxicologists in Japan, 

Korea, Thailand, Brazil and the United States.   

Born in Kyoto, Dr. Ito graduated from 

Nara Medical University, Nara, 1952, received his 

D.Ms. (Ph.D.), 1961, from Osaka University School of 

Medicine, and began his academic faculty career in 

1954. He studied hepatocarcinogenesis from 1962 to 

1964 in the laboratory of Professor Emmanuel Farber, 

University of Pittsburgh. He was very impressed by 

how well equipped the research facility was and the 

overwhelming amount of material available at the 

University of Pittsburgh. His experience in Farber’s 

laboratory very much influenced his fundamental 

research attitude, direction and system after his return 

to Japan.   

In 1972, he became chairman and 

professor at the Department of Oncological Pathology, 

Cancer Center, Nara Medical University, based on his 

extensive and productive research activities. In 1974, 

he became chairman and professor of the First 

Department of Pathology, Nagoya City University 

Medical School, Nagoya, following Professor 

Hisamasa Sato who had been his teacher at Nara 

Medical University. Dr. Ito’s research base was 

anchored to Nagoya thereafter as professor, as Dean 

and then president of the University and continuing as 

Emeritus Professor until his unfortunate terminal 

illness. 

His career as a researcher of in vivo 

chemical carcinogenesis and as a pathologist began 

upon his graduation from Nara Medical University and 

his significant contributions to carcinogenesis, 

toxicology, toxicologic pathology and risk assessment 

cannot be expressed simply by word. He has provided 

the fundamental research needed for the assessment of 

numerous synthetic and natural chemicals that are 

introduced into the environment. He was the first to 

demonstrate carcinogenic activity of many chemicals, 

including α-benzenehexachloride (α-BHC; a pesticide), 

quinoline (industrial chemical), butylated 

hydroxyanisole (BHA; food additive used as an 

antioxidant), catechol (a natural antioxidant), 

2-amino-1-methyl-6-phenylimiazo [4,5-b] pyridine 

(PhIP; meat pyrolysate product) and captafol (a 

pesticide).    Best known for his research on one food 

additive, BHA, this revolutionized the field of 

carcinogenesis research and led to a consensus within 

the scientific community that regulatory actions should 

be decided after thorough examination of both the 

benefit and risk of the chemicals and utilizing all of the 

research available about them, not just relying on the 

outcome of long term rodent bioassays. After his 

publication of the carcinogenicity of BHA, previously 

considered as safe and possibly a chemopreventive 

---

 

2

agent, heated discussions by many experts from U.S.A, 

England, Europe, Canada and Japan took place. It was 

decided not to ban BHA since it is carcinogenic only at 

very high doses, the carcinogenic target organ in 

rodents is the forestomach which humans do not have, 

it is not genotoxic, and it is a very useful food additive 

antioxidant. His1983 report on BHA changed the 

consensus approach regarding risk assessment of 

carcinogenic substances, particularly non-genotoxic 

carcinogens. After his pioneering work with BHA, the 

phrase “before Ito and after Ito” was often used among 

researchers recognizing this landmark decision. After 

discovery of BHA carcinogenicity in rats, Ito’s group 

discovered other natural carcinogenic antioxidants 

present in plants, including catechol, sesamol, caffeic 

acid, hydroquinone and 4-methoxyphenol. The 

research on antioxidants was further extended to 

studies on modification of chemical carcinogenesis by 

antioxidants and led to the conclusion that the 

modification by antioxidants depends upon the target 

organ; an inhibitory effect could occur in one organ but 

enhancement in other organs. 

Dr. Ito also concentrated on developing 

and improving animal models for the study of cancers 

of the prostate, urinary bladder, kidney, stomach, 

intestine and liver. He developed a new in vivo system 

using male rats which is capable of detecting the 

carcinogenicity of chemicals in a relatively short time 

(8 weeks) with high sensitivity and specificity. This 

system, known as the medium-term liver bioassay 

system, was approved as an alternative carcinogenicity 

screening method by the International Conference on 

Harmonization of Technical Requirements for 

Regulation of Pharmaceuticals for Human Use (ICH). 

The system consists of an initial i.p. injection of 

diethylnitrosamine (DEN) as initiator followed by the 

administration of the test compound for 6 weeks 

beginning 2 weeks after the initiation with 2/3 partial 

hepatectomy on week 3. The development of 

preneoplastic lesions in the liver is quantitatively 

analyzed as glutathione S-transferase placental 

(GST-P) form-positive foci by immunohistochemical 

visualization. Dr. Ito’s group has evaluated 313 

chemicals over the past 20 years, with more than 100 

publications reporting the data that demonstrate its 

feasibility and reliability. In addition, he also 

established a multi-organ carcinogenicity screening 

system using rats. 

Dr. Ito was a superb scientist and mentor, 

constantly seeking new ideas, and directing, training 

and mentoring numerous young researchers 

worldwide.  

He had boundless energy and enthusiasm, 

and provided significant leadership for many scientific 

socities in Japan and internationally. In Japan, these 

included the Japanese Society of Toxicologic 

Pathology (JSTP), the Japanese Society of 

Pathology(JSP) and the Japanese Cancer Association 

(JCA). He served as President of JSTP for 5 years, 

developing it as a significant professional society. He 

took charge of office functions and established the 

management and infrastructure of the society. He 

served as president of the annual scientific meeting of 

JSTP in 1987. He was also instrumental in founding 

the International Federation of Societies of Toxicologic 

Pathology (IFSTP), and organized its first international 

conference while he was president in 1992, held in 

Nagoya. This was but one of the many local, national 

and international meetings he organized, always 

memorable for their scientific and social content. He 

was President of the 52nd Annual Meeting of JCA that 

was successfully held in Nagoya in 1994. The Japanese 

Society of Food Chemistry was also one of his major 

areas of effort, serving as president from 1999 to 2002. 

He also contributed in significant ways to the Society 

of Toxicologic Pathology (STP), Society of Toxicology 

(SOT) and the American Association of Cancer 

Research in the U.S.A.   

Recognized internationally for his 

scientific contributions, Dr. Ito was named to 

numerous panels, advisory boards and committees in 

Japan, in the U.S.A. (Food and Drug Administration 

and Environmental Protection Agency), and the 

International Agency for Research on Cancer and 

WHO/FAO Joint Meeting on Pesticide Residues. He 

was also chairman of the Food Safety Committee of 

the Ministry of Health and Welfare, Japan. 

Dr. Ito’s expertise, contributions, and 

sustained excellence were recognized with numerous 

other awards and honors. He received the Award of the 

Princess Takamatsu Cancer Research Fund (1985, 

Tokyo), the Chu-nichi Cultural Award (1985, Nagoya), 

the Robert E. Greenfield Lectureship in 

Carcinogenesis (1989, Omaha, U.S.A), Yomiuri Tokai 

Medical Award (1991, Nagoya), Honorary Doctor of 

science Degree from University of Nebraska Medical 

Center (1994, U.S.A.), Medal with Purple Ribbon 

(1995), the Takeda Prize for Medical Science (1995, 

Osaka), Honorary Doctor of Science Degree from 

University of Cagliari (1996, Italy), Tomizo Yoshida 

Award of JCA (1996, Tokyo), the Kitashi-Mochizuki 

Memorial Award (2002, Shizuoka), and the Order of 

the Sacred Treasure, Gold and Silver Star (2003). 

Throughout his long and distinguished 

career, Dr. Ito has touched and developed a tremendous 

number of scientists in toxicologic pathology, as well 

as in toxicology, pathology, and carcinogenesis. They 

and his family made Ito’s world, and he will be forever 

remembered with gratitude, admiration, respect, and 

friendship.  

 

Tomoyuki Shirai MD., PhD.   

Nagoya City University Graduate School of Medicines, Department of Experimental 

Pathology and Tumor Biology