Carcinogen 발암물질

Carcinogen 발암물질

The term carcinogen refers to any substance, radionuclide or radiation that is an agent directly involved in the promotion of cancer or in the facilitation of its propagation.

This may be due to ability to damage the genome or to the disruption of cellular metabolic processes.

Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit.

Common examples of carcinogens are, inhaled asbestos, certain dioxins, and tobacco smoke.

 

Cancer is a disease where damaged cells of the patient's body do not undergo programmed cell death, but their growth is no longer controlled and their metabolism is altered.

Carcinogens may increase the risk of getting cancer by altering cellular metabolism or damaging DNA directly in cells, which interferes with biological processes, and induces the uncontrolled, malignant division, ultimately leading to the formation of tumors. Usually DNA damage, if too severe to repair, leads to programmed cell death, but if the programmed cell death pathway is damaged, then the cell cannot prevent itself from becoming a cancer cell.

 

There are many natural carcinogens. Aflatoxin B1, which is produced by the fungus Aspergillus flavus growing on stored grains, nuts and peanut butter, is an example of a potent, naturally-occurring microbial carcinogen.

 

Certain viruses such as Hepatitis B and human papilloma viruses have been found to cause cancer in humans.

 

The first one shown to cause cancer in animals is Rous sarcoma virus, discovered in 1910 by Peyton Rous.

 

Benzene, kepone, EDB, asbestos, and the waste rock of oil shale mining have all been classified as carcinogenic.

 

As far back as the 1930s, industrial smoke and tobacco smoke were identified as sources of dozens of carcinogens, including benzopyrene, tobacco-specific nitrosamines such as nitrosonornicotine, and reactive aldehydes such as formaldehyde — which is also a hazard in embalming and making plastics.

 

Vinyl chloride, from which PVC is manufactured, is a carcinogen and thus a hazard in PVC production.

 

Co-carcinogens are chemicals that do not separately cause cancer, but do so in specific combinations.

 

After the carcinogen enters the body, the body makes an attempt to eliminate it through a process called biotransformation. The purpose of these reactions is to make the carcinogen more water-soluble so that it can be removed from the body. But these reactions can also convert a less toxic carcinogen into a more toxic one.

 

DNA is nucleophilic, therefore soluble carbon electrophiles are carcinogenic, because DNA attacks them. For example, some alkenes are toxicated by human enzymes to produce an electrophilic epoxide. DNA attacks the epoxide, and is bound permanently to it. This is the mechanism behind the carcinogenity of benzopyrene in tobacco smoke, other aromatics, aflatoxin and mustard gas.

 

 

 Radiation
CERCLA identifies all radionuclides as carcinogens, although the nature of the emitted radiation (alpha, beta, or gamma, and the energy), its consequent capacity to cause ionization in tissues, and the magnitude of radiation exposure, determine the potential hazard. Carcinogenity of radiation depends of the type of radiation, type of exposure and penetration. For example, alpha radiation has low penetration and is not a hazard outside the body, but are carcinogenic when inhaled or ingested.

For example, Thorotrast, a (incidentally-radioactive) suspension previously used as a contrast medium in x-ray diagnostics, is a potent human carcinogen known because of its retention within various organs and persistent emission of alpha particles. Marie Curie, one of the pioneers of radioactivity, died of cancer caused by radiation exposure during her experiments.

Not all types of electromagnetic radiation are in fact carcinogenic. Low-energy waves on the electromagnetic spectrum are generally not, including radio waves, microwave radiation, infrared radiation, and visible light. Higher-energy radiation, including ultraviolet radiation (present in sunlight), x-rays, and gamma radiation, generally is carcinogenic, if received in sufficient doses.

Substances or foods irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic. No "radiation" remains, just like no light remains in a lens. (In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can make substances radioactive.)

 

 Carcinogens in prepared food
Cooking food at high temperatures, for example broiling or barbecuing meats, can lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., benzopyrene).[1] Charring of food resembles coking and tobacco pyrolysis, and produces similar carcinogens. There are several carcinogenic pyrolysis products, such as polynuclear aromatic hydrocarbons, which are converted by human enzymes into epoxides, which attach permanently to DNA. Pre-cooking meats in a microwave oven for 2-3 minutes before broiling shortens the time on the hot pan, and removes heterocyclic amine (HCA) precursors, which can help minimize the formation of these carcinogens.[2]

Reports from the Food Standards Agency have found that the known animal carcinogen acrylamide is generated in fried or overheated carbohydrate foods (such as french fries and potato chips).[3] Studies are underway at the FDA and European regulatory agencies to assess its potential risk to humans. The charred residue on barbecued meats has been identified as a carcinogen, along with many other tars.

Nevertheless, the fact that the food contains minute quantities does not necessarily mean that there is a significant hazard. The gastrointestinal tract sheds its outer layer continuously to protect itself from carcinomas, and has a high activity of detoxifying enzymes.

 

 

 

 Classification of carcinogens
Carcinogens can be classified as genotoxic or nongenotoxic. Genotoxins cause irreversible genetic damage or mutations by binding to DNA. Genotoxins include chemical agents like N-Nitroso-N-Methylurea (MNU) or non-chemical agents such as ultraviolet light and ionizing radiation. Certain viruses can also act as carcinogens by interacting with DNA.

Nongenotoxins do not directly affect DNA but act in other ways to promote growth. These include hormones and some organic compounds.[4]

 

 IARC classification of carcinogens
Group 1: the agent (mixture) is definitely carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
Group 2A: the agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
Group 2B: the agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
Group 3: the agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans.
Group 4: the agent (mixture) is probably not carcinogenic to humans.
Further details can be found in the IARC Monographs.

 

Procarcinogen
A procarcinogen is a precursor to a carcinogen. one example is nitrites, for example when taken in by the diet. They are not carcinogenic themselves, but turn into nitrosamines in the body, which are carcinogenic.

 

 

 

 최근까지 인체에서 우발적으로 암을 발생시킨 발암물질의 수는 22종으로 알려져 있으며, 동물실험에서 증명된 발암물질의 수는 약 1,500종에 달하고 있다. 각종 발암물질의 검출에 있어서 체세포염색체의 변이(變異) 또는 미생물의 돌연변이 유발을 통한 검사법이 널리 사용되고 있으나, 최종적으로 사람과 유사한 감수성을 나타내는 동물을 사용하여 발암성을 실제로 증명하게 되었다.

 

발암물질은 외인성(外因性) 발암물질과 내인성 발암물질로 나눌 수 있다.

 

외인성 발암물질의 90% 이상이 자연환경의 화학물질로 밝혀져 있다. 분류 및 종류로는 다음과 같다.

 

⑴ 방향족 탄화수소:

DMBA(7, 12-dimethylbenz[α]anthracene, 9, 10-dimethyl-1, 2-benzanthracene)와 벤조[α]피렌 등이 대표적인 것으로, 벤조[α]피렌은 실험동물 투여 시 강력한 발암물질로, 배기가스·공장매연·담배연기 등에서 검출되며, 숯불고기에는 lkg당 50μg이 검출된다.

 

⑵ 방향족 아민류 및 관련 나이트로 화합물:

대표적인 것으로 4-아미노바이페닐, 2-나프틸아민, 벤지딘 등이 있으며, 인체의 방광암 발생 원인물질로서 주로 색소와 염료 등에 존재하며, 실험동물에 투여하면 방광암과 간암 발생률이 높은 것으로 알려져 있다.

 

⑶ 방향족 아조화합물과 그 유사체:

DAB(4-dimethylaminoazobenzene, butter yellow), 3-메톡시-4-아미노아조벤젠, 폰소(ponceau)MX, 4-아미노아조벤젠 등이 있으며, DAB는 각종 아조색소의 대표적 발암물질로 간암을 일으킨다는 것이 밝혀졌으며, 이 계열의 발암물질은 착색료 등에 존재한다.

 

⑷ 아민과 아조화합물을 제외한 화합물(헤테로고리 화합물):

4-나이트로퀴놀린-1-옥시드, 벤즈[c]아크리딘, 2-(2-푸릴)-3-(5-나이트로-2-푸릴)아크릴아마이드, 쿠마린(coumarin) 등이 있으며, 일명 AF-2라고 하는 2-(2-푸릴)-3-(5-나이트로-2-푸릴)아크릴아마이드의 경우는 1965년 합성 방부제로서 식품첨가물로 허가되었으나, 발암성이 알려져 1974년에 취소되었다.

 

⑸ N-나이트로소 화합물을 제외한 지방족화합물:

사염화탄소 CCl4, 둘신, 에틸카바메이트(우레탄), 머스터드 가스, 트리스-(1-아지리디닐)포스핀옥시드, 1,4-뷰타네다이올다이메탄설포네이트(뷰설판), 아자세린, 다이에틸스틸베스톨 등이 있으며,

둘신은 인공 감미료나 혈색소를 메트헤모글로빈으로 전환시키는 혈액독(血液毒)이 있다고 알려졌고, 실험용 쥐에 투여한 결과 간암이 발생하였으므로 사용이 금지되었다.

우레탄은 이 계열에서 가장 강력한 발암물질로 폐암·림프종(腫)·간암·악성흑색종·혈관종·피부암 등을 일으킨다.

 

⑹ N-나이트로소 화합물:

이 계열의 발암물질이 주목되고 있는 이유는 N-나이트로소 화합물의 전구체(前驅體)가 아질산염과 각종 2급 아민류에 있고, 이들이 생활환경에 다수 존재하며, 위장 내에서 이들 물질이 반응을 일으켜 N-나이트로소 화합물을 생성하고, 또한 대다수의 화합물이 여러 종족의 실험동물에서 발암성 관찰이 쉬우며 발암효과가 크게 나타나는 등 여러 가지 요인에 의해 인간의 암 관찰에서 이정표가 되고 있다는 데 있다.

종류로는 DMN(N-nitrosodimethylamine: 간암), DBN(N-nitroso-di-n-butylamine: 방광암), NMU(nitrosomethylurea: 림프종·폐암), ENU(nitrosoethylurea: 신장암·신경종양), NBU(nitrosobutylurea: 백혈병), MNNG(N-methyl-N'-intro-N-nitrosoguanidine: 위암) 등이 있다.

 

⑺ 무기화합물:

비소·카드뮴·크로뮴·니켈·납·베릴륨·철·석면 등이 있고

역학적으로는 산업성 노출 근로자에서 석면·크로뮴·니켈 화합물에 의해 특정한 암의 발생이 증가되고 있음이 알려져 있다.

 

⑻ 유기 할로젠화합물:

BHC(공업용), 알드린, DDT, PCB(polychlorinated biphenyl) 등은 살충제·공업용 화합물로서 생활환경에 도입되어 주로 간종양을 발생시키며, 이 밖에도 클로람페니콜과 같은 항생물질로서 인체에서 재생불능성 빈혈 및 백혈병을 유발하는 것이 있다.

 

⑼ 천연산물:

식품의 곰팡이 오염으로 발생하는 아플라톡신류와, 이 밖에 악티노마이신·도노마이신 등 항생물질, 시카린·타닌산·고사리 등이 있다.

아플라톡신은 간암 원인물질이며,

곰팡이의 대사산물(代謝産物)로 때로는 메주와 된장 속에서 검출된 바 있고,

고사리는 가축에서 방광암을 일으키는 것으로 알려져 있다.

 

⑽ 방사성 동위원소와 방사선:

X선·라듐·코발트 60·아스타틴 211·아이오딘 131·칼슘 45 등이 있다.

 

⑾ 물리적 발암물질:

일광·열화상(熱火傷)·자외선·플라스틱·우주선 등으로, 피부암을 주로 발생시킨다.