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4,4'-Diaminodiphenylmethane: promoting effect on the development of thyroid tumors in rats treated with
Abstract:
4,4'-Diaminodiphenylmethane (4,4'-methylenedianiline) (DDPM) promoted the development of thyroid tumors in rats treated with a subeffective dose of N-bis(2-hydroxypropyl)nitrosamine (2,2'-dihydroxy-N-nitrosodipropylamine) (DHPN) for thyroid tumorigenesis. Male inbred W rats were given a single ip injection of 280 mg DHPN/100 g body weight and fed diets with or without 1,000 ppm DDPM. Thyroid tumor incidences at the end of week 20 of the experiment were 90% (19/21) in rats given DHPN and then DDPM and 28% (6/21) in rats given DHPN alone. The incidence of thyroid cancers was 9.5% (2/21) in rats first given DHPN and then DDPM. Untreated rats and rats given DDPM alone had no thyroid tumors after 20 weeks. Incidences of kidney tumors were 38% (8/21) in rats given DHPN and then DDPM and 28% (6/21) in rats given DHPN alone. No tumors were found in the kidneys and lungs of rats given DDPM alone and in those of control rats. Treatment with DDPM alone slightly but not significantly decreased the serum concentrations of thyroxine and triiodothyronine; treatment with DHPN plus DDPM had no such effect.
Insights
4,4'-Diaminodiphenylmethane (DDPM) significantly increased thyroid tumor development in rats exposed to N-bis(2-hydroxypropyl)nitrosamine (DHPN). This study highlights DDPM as a promoter of DHPN-induced thyroid tumorigenesis.
Area of Science:
- Toxicology
- Carcinogenesis
- Endocrinology
Background:
- Thyroid tumorigenesis is a complex process influenced by various chemical agents.
- N-bis(2-hydroxypropyl)nitrosamine (DHPN) is a known inducer of thyroid tumors in rodents.
- The role of co-exposures in modulating carcinogen effects requires further investigation.
Purpose of the Study:
- To investigate the potential co-carcinogenic or promoting effects of 4,4 '-Diaminodiphenylmethane (DDPM) on DHPN-induced thyroid tumorigenesis in rats.
- To evaluate the impact of DDPM on tumor incidence in other organs, specifically the kidneys.
- To assess the influence of DDPM on thyroid hormone levels.
Main Methods:
- Male inbred W rats were administered a single intraperitoneal injection of DHPN.
- Rats were subsequently fed diets containing either 1,000 ppm DDPM or no DDPM for 20 weeks.
- Tumor incidence in the thyroid and kidneys was assessed, along with serum concentrations of thyroxine and triiodothyronine.
Main Results:
- Thyroid tumor incidence was significantly higher (90%) in rats treated with DHPN followed by DDPM compared to DHPN alone (28%).
- A small incidence of thyroid cancer (9.5%) was observed in the DHPN + DDPM group.
- Kidney tumor incidences were 38% for DHPN + DDPM and 28% for DHPN alone; no tumors were observed in control or DDPM-only groups.
- DDPM alone caused a slight, non-significant decrease in thyroxine and triiodothyronine levels.
Conclusions:
- 4,4 '-Diaminodiphenylmethane (DDPM) acts as a promoter in DHPN-induced thyroid tumorigenesis in rats.
- DDPM exposure did not significantly alter DHPN's effect on kidney tumor development.
- These findings underscore the importance of considering co-exposures in toxicological risk assessments.